Product Name

  • Name

    2-AZETIDINONE, 1-(4-FLUOROPHENYL)-3-[(3S)-3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4-[4-(PHENYLMETHOXY)PHENYL]-, (3R,4S)-

  • EINECS
  • CAS No. 163222-32-0
  • Article Data40
  • CAS DataBase
  • Density 1.271 g/cm3
  • Solubility
  • Melting Point
  • Formula C31H27F2NO3
  • Boiling Point 706.462 °C at 760 mmHg
  • Molecular Weight 499.557
  • Flash Point 381.055 °C
  • Transport Information
  • Appearance Off-white solid
  • Safety
  • Risk Codes
  • Molecular Structure Molecular Structure of 163222-32-0 (2-AZETIDINONE, 1-(4-FLUOROPHENYL)-3-[(3S)-3-(4-FLUOROPHENYL)-3-HYDROXYPROPYL]-4-[4-(PHENYLMETHOXY)PHENYL]-, (3R,4S)-)
  • Hazard Symbols
  • Synonyms 2-Azetidinone,1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-hydroxypropyl]-4-[4-(phenylmethoxy)phenyl]-,[3R-[3a(S*),4b]]-;(3R,4S)-4-[(4-Benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-2-azetidinone;1-(4-Fluorophenyl)-3(R)-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4(S)-(4-benzyloxyphenyl)azetidin-2-one;
  • PSA 49.77000
  • LogP 6.82670

Synthetic route

(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one
190595-65-4

(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
With formic acid; [(S,S)-teth-TsDpen RuCl]; triethylamine In ethylbenzene at 35 - 40℃; for 24h; Inert atmosphere;99.8%
With methanesulfonic acid; dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran; methyl tertiarybutylether; toluene at -25 - -20℃; for 2.5 - 3.5h; Product distribution / selectivity;98.04%
With methanesulfonic acid; dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran; toluene at -25 - -20℃; for 2.5 - 3.5h; Product distribution / selectivity;98.6%
benzyl bromide
100-39-0

benzyl bromide

ezetemibe
163222-33-1

ezetemibe

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
With caesium carbonate In N,N-dimethyl-formamide at 20℃; for 3h;99%
(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one
190595-65-4

(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one

A

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

B

(3R,4S,3'R)-1-(4-fluorophenyl)-4-(4-hydroxyphenyl)-3-[3'-(4-fluorophenyl)-3'-hydroxy-propyl]-azetidin-2-one
163380-15-2

(3R,4S,3'R)-1-(4-fluorophenyl)-4-(4-hydroxyphenyl)-3-[3'-(4-fluorophenyl)-3'-hydroxy-propyl]-azetidin-2-one

Conditions
ConditionsYield
With dimethylsulfide borane complex In tetrahydrofuran at 22℃; for 3h;A 0.141 g
B n/a
With dimethylsulfide borane complex In tetrahydrofuran at 22℃; for 3h;
Stage #1: (3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one With sodium tetrahydroborate; chloro-trimethyl-silane; (R)-α,α-diphenylprolinol In tetrahydrofuran at 19 - 22℃; for 2.78333h; Heating / reflux;
Stage #2: With hydrogenchloride; water In tetrahydrofuran; toluene at 2℃; for 0.5h; Product distribution / selectivity;		A n/a
B n/a
With 1,1,1,3',3',3'-hexafluoro-propanol; C32H39BrMnN2O2P; potassium tert-butylate; hydrogen In methanol at 20℃; under 22502.3 Torr; for 16h; Glovebox; Autoclave; Overall yield = 99 %; enantioselective reaction;A n/a
B n/a
With C32H39BrMnN2O2P; potassium tert-butylate; hydrogen In methanol at 20℃; under 22502.3 Torr; for 16h; Glovebox; Autoclave; Optical yield = 85 percent ee; enantioselective reaction;
4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine
70627-52-0

4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 6 steps
1: 64 percent / LDA; DMPU; LiCl / dimethylformamide; tetrahydrofuran / 18 h / -30 - -25 °C
2: 90 percent / NaIO4 / acetonitrile; H2O / 2 h / 20 °C
3: BF3 etherate / toluene / 0.08 h / -30 °C
4: 99 g / p-toluenesulfonic acid monohydrate; molecular sieves / toluene / 4 h / 40 - 50 °C
5: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
6: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
Multi-step reaction with 4 steps
1: N-ethyl-N,N-diisopropylamine; titanium(IV) isopropylate; titanium tetrachloride / dichloromethane / 3 h / -5 °C
2: N,O-Bis(trimethylsilyl)acetamide; tetrabutyl ammonium fluoride / toluene / 48 h / Reflux
3: formic acid / dichloromethane / 12 h / Reflux
4: dimethyl sulfide borane / dichloromethane; toluene; tetrahydrofuran / 12 h / 15 °C
View Scheme
Multi-step reaction with 2 steps
1: N,O-bis-(trimethylsilyl)-acetamide; tetrabutyl ammonium fluoride / toluene / 60 °C
2: dimethylsulfide borane complex / dichloromethane; toluene / 3 h / -5 - 0 °C / Inert atmosphere
View Scheme
(2S,3S)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxazetidine-3-carbaldehyde
221349-58-2

(2S,3S)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxazetidine-3-carbaldehyde

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: BF3 etherate / toluene / 0.08 h / -30 °C
2: 99 g / p-toluenesulfonic acid monohydrate; molecular sieves / toluene / 4 h / 40 - 50 °C
3: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
4: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
(3S,4S)-4-(4-Benzyloxy-phenyl)-3-((S)-1,2-dihydroxy-ethyl)-1-(4-fluoro-phenyl)-azetidin-2-one
221349-56-0

(3S,4S)-4-(4-Benzyloxy-phenyl)-3-((S)-1,2-dihydroxy-ethyl)-1-(4-fluoro-phenyl)-azetidin-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: 90 percent / NaIO4 / acetonitrile; H2O / 2 h / 20 °C
2: BF3 etherate / toluene / 0.08 h / -30 °C
3: 99 g / p-toluenesulfonic acid monohydrate; molecular sieves / toluene / 4 h / 40 - 50 °C
4: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
5: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
lithium; 1-(4-fluoro-phenyl)-ethenolate

lithium; 1-(4-fluoro-phenyl)-ethenolate

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: BF3 etherate / toluene / 0.08 h / -30 °C
2: 99 g / p-toluenesulfonic acid monohydrate; molecular sieves / toluene / 4 h / 40 - 50 °C
3: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
4: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
(3R,4S)-4-(4-Benzyloxy-phenyl)-1-(4-fluoro-phenyl)-3-[(E)-3-(4-fluoro-phenyl)-3-oxo-propenyl]-azetidin-2-one
221349-60-6

(3R,4S)-4-(4-Benzyloxy-phenyl)-1-(4-fluoro-phenyl)-3-[(E)-3-(4-fluoro-phenyl)-3-oxo-propenyl]-azetidin-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
2: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
(3S,4S)-4-(4-Benzyloxy-phenyl)-1-(4-fluoro-phenyl)-3-[3-(4-fluoro-phenyl)-1-hydroxy-3-oxo-propyl]-azetidin-2-one
231301-00-1

(3S,4S)-4-(4-Benzyloxy-phenyl)-1-(4-fluoro-phenyl)-3-[3-(4-fluoro-phenyl)-1-hydroxy-3-oxo-propyl]-azetidin-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: 99 g / p-toluenesulfonic acid monohydrate; molecular sieves / toluene / 4 h / 40 - 50 °C
2: 71 percent / (PPh3)3RhCl; hydrogen / CH2Cl2 / 18 h / 3102.89 Torr
3: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C
View Scheme
(Z)-1-(4-(benzyloxy)phenyl)-N-(4-fluorophenyl)methaneimine
219653-96-0

(Z)-1-(4-(benzyloxy)phenyl)-N-(4-fluorophenyl)methaneimine

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 5 steps
1: (nBu)3N / heptane; toluene / 80 - 90 °C
2: LiOH*H2O / methanol / 2 h
3: oxalyl chloride / CH2Cl2 / 16 h / 22 °C
4: (Ph3P)4Pd / tetrahydrofuran / 1 h / 10 °C
5: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C
View Scheme
(3R,4S)-1-(4-fluorophenyl)-3-(3-hydroxy-3-oxopropyl)-4-(4-benzyloxyphenyl)-2-azetidinone
204589-82-2

(3R,4S)-1-(4-fluorophenyl)-3-(3-hydroxy-3-oxopropyl)-4-(4-benzyloxyphenyl)-2-azetidinone

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: oxalyl chloride / CH2Cl2 / 16 h / 22 °C
2: (Ph3P)4Pd / tetrahydrofuran / 1 h / 10 °C
3: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C
View Scheme
3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl)azetidin-3-yl)propionic acid chloride
204589-84-4

3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl)azetidin-3-yl)propionic acid chloride

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: (Ph3P)4Pd / tetrahydrofuran / 1 h / 10 °C
2: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C
View Scheme
methyl 3-((2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoate
204589-80-0

methyl 3-((2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoate

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: LiOH*H2O / methanol / 2 h
2: oxalyl chloride / CH2Cl2 / 16 h / 22 °C
3: (Ph3P)4Pd / tetrahydrofuran / 1 h / 10 °C
4: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C
View Scheme
Multi-step reaction with 3 steps
1.1: diethyl aluminiumcholoride / toluene / -12 - 20 °C / Inert atmosphere
2.1: magnesium / tetrahydrofuran / 1 h / 40 - 50 °C / Inert atmosphere
2.2: 1 h / -5 - 0 °C
3.1: [(S,S)-teth-TsDpen RuCl]; triethylamine; formic acid / ethylbenzene / 24 h / 35 - 40 °C / Inert atmosphere
View Scheme
[14C]-Sch 57871
191330-56-0

[14C]-Sch 57871

(3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole
112022-83-0

(3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Stage #1: [14C]-Sch 57871; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran at -20℃; for 0.0833333h;
Stage #2: With dimethylsulfide borane complex In tetrahydrofuran at -20℃; for 1.5h;
1-(4-fluorophenyl)-4(S)-(4-hydroxyphenyl)-3(R)-(3-oxo-3-phenylpropyl)-2-azetidinone
163222-31-9

1-(4-fluorophenyl)-4(S)-(4-hydroxyphenyl)-3(R)-(3-oxo-3-phenylpropyl)-2-azetidinone

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
With dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran at -20℃; for 1.5h;
methanol
67-56-1

methanol

(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one
190595-65-4

(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one

(3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole
112022-83-0

(3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
With hydrogenchloride In tetrahydrofuran
...Expand
1-Bromo-4-fluorobenzene
460-00-4

1-Bromo-4-fluorobenzene

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: magnesium; Bis<2-(N,N-dimethylamino)aethyl>aether / 0.5 h / 0 °C
2.1: (R)-1,1'-Bi-2-naphthol / titanium(IV) isopropylate / diethyl ether; tetrahydrofuran / 1.5 h / 0 - 25 °C
2.2: -20 - 25 °C
2.3: 0 °C
View Scheme
Multi-step reaction with 2 steps
1.1: magnesium / tetrahydrofuran / 1 h / 40 - 50 °C / Inert atmosphere
1.2: 1 h / -5 - 0 °C
2.1: [(S,S)-teth-TsDpen RuCl]; triethylamine; formic acid / ethylbenzene / 24 h / 35 - 40 °C / Inert atmosphere
View Scheme
3-[(2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]propanal
1412967-16-8

3-[(2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]propanal

4-flourophenylmagnesium bromide
352-13-6

4-flourophenylmagnesium bromide

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Stage #1: 4-flourophenylmagnesium bromide With (R)-1,1'-Bi-2-naphthol; titanium(IV) isopropylate In tetrahydrofuran; diethyl ether at 0 - 25℃; for 1.5h;
Stage #2: 3-[(2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]propanal In tetrahydrofuran; diethyl ether at -20 - 25℃;
Stage #3: With hydrogenchloride; water In tetrahydrofuran; diethyl ether at 0℃;
(3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-hydroxypropyl)azetidin-2-one
1412967-14-6

(3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-hydroxypropyl)azetidin-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1.1: sodium hydrogencarbonate; sodium hypochlorite; potassium bromide; 2,2,6,6-Tetramethyl-1-piperidinyloxy free radical / Difluoromethane / 25 °C / Cooling with ice
2.1: (R)-1,1'-Bi-2-naphthol / titanium(IV) isopropylate / diethyl ether; tetrahydrofuran / 1.5 h / 0 - 25 °C
2.2: -20 - 25 °C
2.3: 0 °C
View Scheme
(1'R,6R)-3-[(4-benzyloxyphenyl)-(4-fluorophenylamino)-methyl]-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one
1416263-33-6

(1'R,6R)-3-[(4-benzyloxyphenyl)-(4-fluorophenylamino)-methyl]-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: lithium hydroxide / tetrahydrofuran; water / 18 h
2: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
3: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(1'S,3R,6S)-3-[(4-benzyloxyphenyl)-(4-fluorophenylamino)-methyl]-6-(4-fluorophenyl)-tetrahydro-2H-pyran-2-one
1416263-36-9

(1'S,3R,6S)-3-[(4-benzyloxyphenyl)-(4-fluorophenylamino)-methyl]-6-(4-fluorophenyl)-tetrahydro-2H-pyran-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
With tert-butylmagnesium chloride In diethyl ether at 0℃; for 2h;
(3S,3aS,6S,7aS)-3-(4-(benzyloxy)phenyl)-2,6-bis(4-fluorophenyl)tetrahydro-2H-pyrano[3,4-d]isoxazol-4(6H)-one
1416263-37-0

(3S,3aS,6S,7aS)-3-(4-(benzyloxy)phenyl)-2,6-bis(4-fluorophenyl)tetrahydro-2H-pyrano[3,4-d]isoxazol-4(6H)-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 4 steps
1: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
2: Burgess Reagent / toluene / 18 h / 90 °C
3: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
4: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(R)-2,3-dihydro-2-(4-fluorophenyl)-4H-pyran-4-one

(R)-2,3-dihydro-2-(4-fluorophenyl)-4H-pyran-4-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 10 steps
1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
2: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
3: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
4: toluene / 72 h / Reflux
5: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
6: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
7: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
8: Burgess Reagent / toluene / 18 h / 90 °C
9: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
10: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 10 steps
1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
2: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
3: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
4: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
5: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
6: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
7: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
8: Burgess Reagent / toluene / 18 h / 90 °C
9: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
10: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
2.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
3.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
4.1: toluene / 72 h / Reflux
5.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
6.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
6.2: 0.25 h / 20 °C
7.1: lithium hydroxide / tetrahydrofuran; water / 18 h
8.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
9.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
2.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
3.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
4.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
5.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
6.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
6.2: 0.25 h / 20 °C
7.1: lithium hydroxide / tetrahydrofuran; water / 18 h
8.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
9.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(3S,4S,6S)-3-((S)-(4-(benzyloxy)phenyl)(4-fluorophenylamino)methyl)-6-(4-fluorophenyl)-4-hydroxytetrahydro-2H-pyran-2-one

(3S,4S,6S)-3-((S)-(4-(benzyloxy)phenyl)(4-fluorophenylamino)methyl)-6-(4-fluorophenyl)-4-hydroxytetrahydro-2H-pyran-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 3 steps
1: Burgess Reagent / toluene / 18 h / 90 °C
2: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
3: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(6S)-3-((R)-(4-(benzyloxy)phenyl)(4-fluorophenylamino)-methyl)-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one
1416263-38-1

(6S)-3-((R)-(4-(benzyloxy)phenyl)(4-fluorophenylamino)-methyl)-6-(4-fluorophenyl)-5,6-dihydro-2H-pyran-2-one

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
2: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
4-fluorobenzaldehyde
459-57-4

4-fluorobenzaldehyde

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 10 steps
1.1: [(R,R)-salen-Cr]BF4 / tert-butyl methyl ether / 24 h / -30 °C / Molecular sieve
1.2: 5 h / 20 °C
2.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
3.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
4.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
5.1: toluene / 72 h / Reflux
6.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
7.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
7.2: 0.25 h / 20 °C
8.1: lithium hydroxide / tetrahydrofuran; water / 18 h
9.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
10.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 10 steps
1.1: [(R,R)-salen-Cr]BF4 / tert-butyl methyl ether / 24 h / -30 °C / Molecular sieve
1.2: 5 h / 20 °C
2.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
3.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
4.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
5.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
6.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
7.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
7.2: 0.25 h / 20 °C
8.1: lithium hydroxide / tetrahydrofuran; water / 18 h
9.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
10.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 11 steps
1.1: [(R,R)-salen-Cr]BF4 / tert-butyl methyl ether / 24 h / -30 °C / Molecular sieve
1.2: 5 h / 20 °C
2.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
3.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
4.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
5.1: toluene / 72 h / Reflux
6.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
8.1: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
9.1: Burgess Reagent / toluene / 18 h / 90 °C
10.1: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
11.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 11 steps
1.1: [(R,R)-salen-Cr]BF4 / tert-butyl methyl ether / 24 h / -30 °C / Molecular sieve
1.2: 5 h / 20 °C
2.1: cerium(III) chloride heptahydrate; sodium tetrahydroborate / dichloromethane; methanol / 0.5 h / -20 °C
3.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
4.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
5.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
6.1: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
8.1: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
9.1: Burgess Reagent / toluene / 18 h / 90 °C
10.1: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
11.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(2R)-2-(4-fluorophenyl)-3,4-dihydro-2H-pyran-4-ol
1416263-27-8

(2R)-2-(4-fluorophenyl)-3,4-dihydro-2H-pyran-4-ol

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
2.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
3.1: toluene / 72 h / Reflux
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 8 steps
1.1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
2.1: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
3.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
2: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
3: toluene / 72 h / Reflux
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: dihydrogen peroxide; molybdenum(VI) oxide / acetonitrile / 24 h
2: pyridine; acetic anhydride / dichloromethane / 2 h / 20 °C
3: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
4-hydroxy-benzaldehyde
123-08-0

4-hydroxy-benzaldehyde

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1.1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2.1: methanesulfonic acid / acetone / 2 h / 20 °C
3.1: toluene / 72 h / Reflux
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 8 steps
1.1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2.1: methanesulfonic acid / acetone / 2 h / 20 °C
3.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2: methanesulfonic acid / acetone / 2 h / 20 °C
3: toluene / 72 h / Reflux
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2: methanesulfonic acid / acetone / 2 h / 20 °C
3: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 5 steps
1.1: potassium carbonate / 12 h / 20 °C
1.2: 4 h / Reflux
2.1: N-ethyl-N,N-diisopropylamine; titanium(IV) isopropylate; titanium tetrachloride / dichloromethane / 3 h / -5 °C
3.1: N,O-Bis(trimethylsilyl)acetamide; tetrabutyl ammonium fluoride / toluene / 48 h / Reflux
4.1: formic acid / dichloromethane / 12 h / Reflux
5.1: dimethyl sulfide borane / dichloromethane; toluene; tetrahydrofuran / 12 h / 15 °C
View Scheme
benzyl chloride
100-44-7

benzyl chloride

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 8 steps
1.1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2.1: methanesulfonic acid / acetone / 2 h / 20 °C
3.1: toluene / 72 h / Reflux
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 8 steps
1.1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2.1: methanesulfonic acid / acetone / 2 h / 20 °C
3.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
5.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
5.2: 0.25 h / 20 °C
6.1: lithium hydroxide / tetrahydrofuran; water / 18 h
7.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
8.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2: methanesulfonic acid / acetone / 2 h / 20 °C
3: toluene / 72 h / Reflux
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 9 steps
1: potassium carbonate; potassium iodide / tetrahydrofuran / 20 h / Reflux
2: methanesulfonic acid / acetone / 2 h / 20 °C
3: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
4: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
5: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
6: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
7: Burgess Reagent / toluene / 18 h / 90 °C
8: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
9: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
p-benzyloxybenzaldehyde
4397-53-9

p-benzyloxybenzaldehyde

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 7 steps
1.1: methanesulfonic acid / acetone / 2 h / 20 °C
2.1: toluene / 72 h / Reflux
3.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
4.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
4.2: 0.25 h / 20 °C
5.1: lithium hydroxide / tetrahydrofuran; water / 18 h
6.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
7.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 7 steps
1.1: methanesulfonic acid / acetone / 2 h / 20 °C
2.1: scandium tris(trifluoromethanesulfonate) / toluene / 72 h / 30 °C / Molecular sieve
3.1: potassium iodide; chloro-trimethyl-silane / acetonitrile / 0.58 h / 20 °C
4.1: chloro-trimethyl-silane; 1H-imidazole / dichloromethane / 0.5 h / 20 °C
4.2: 0.25 h / 20 °C
5.1: lithium hydroxide / tetrahydrofuran; water / 18 h
6.1: triphenylphosphine; di-isopropyl azodicarboxylate / 3 h / 0 °C
7.1: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
Multi-step reaction with 8 steps
1: methanesulfonic acid / acetone / 2 h / 20 °C
2: toluene / 72 h / Reflux
3: lithium hydroxide monohydrate / tetrahydrofuran; water / 18 h
4: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 3 h / 0 °C
5: potassium iodide / acetonitrile; water / 0.58 h / 20 °C
6: Burgess Reagent / toluene / 18 h / 90 °C
7: platinum(IV) oxide; hydrogen / toluene / 20 °C / 750.08 Torr
8: tert-butylmagnesium chloride / diethyl ether / 2 h / 0 °C
View Scheme
(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

ezetemibe
163222-33-1

ezetemibe

Conditions
ConditionsYield
With 10 wt% Pd(OH)2 on carbon; hydrogen In methanol; cyclohexane at 70℃; under 760.051 Torr; for 3h;99%
With 5%-palladium/activated carbon; hydrogen In tetrahydrofuran; ethanol at 50 - 55℃; under 37.5038 - 75.0075 Torr;90.3%
With palladium 10% on activated carbon; ammonium formate; acetic acid for 6h; Reflux;90%
L-N-Boc-Ala
15761-38-3

L-N-Boc-Ala

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

(1S)-3-[(2S,3R)-2-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]-1-(4-fluorophenyl)propyl (2S)-2-{[(tert-butoxy)carbonyl]amino}propanoate

(1S)-3-[(2S,3R)-2-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]-1-(4-fluorophenyl)propyl (2S)-2-{[(tert-butoxy)carbonyl]amino}propanoate

Conditions
ConditionsYield
With dmap; dicyclohexyl-carbodiimide In dichloromethane Inert atmosphere;69%
(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

1-(4-fluorophenyl)-(3R)-[(4-fluorophenyl)-(2E)-propenyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone

1-(4-fluorophenyl)-(3R)-[(4-fluorophenyl)-(2E)-propenyl]-(4S)-(4-hydroxyphenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: H2 / 10percent Pd/C / ethanol / 16 h / 3102.9 Torr
2: p-TsOH*H2O / toluene / 6 h / 80 °C
View Scheme
(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

4(S)-(4-acetyloxyphenyl)-3(R)-(3(S)-acetyloxy-3-(4-fluorophenyl)propyl)-1-(4-fluorophenyl)-2-azetidinone
163380-20-9

4(S)-(4-acetyloxyphenyl)-3(R)-(3(S)-acetyloxy-3-(4-fluorophenyl)propyl)-1-(4-fluorophenyl)-2-azetidinone

Conditions
ConditionsYield
Multi-step reaction with 2 steps
1: H2 / 10percent Pd/C / ethanol / 16 h / 3102.9 Torr
2: 0.260 g / pyridine / CH2Cl2 / 1 h / 22 °C
View Scheme
(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone
163222-32-0

(3R,4S)-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3(S)-hydroxypropyl]-4-(4-benzyloxyphenyl)-2-azetidinone

A

EZT-FAM
1197811-72-5

EZT-FAM

B

ezetemibe
163222-33-1

ezetemibe

Conditions
ConditionsYield
With formic acid; ammonium formate; 5%-palladium/activated carbon In methanol at 20℃; Product distribution / selectivity; Inert atmosphere;

(3R,4S)-1-(4-Fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-[4-(phenylmethoxy)phenyl]-2-azetidinone Specification

The (3R,4S)-1-(4-Fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-[4-(phenylmethoxy)phenyl]-2-azetidinone, with the CAS registry number 163222-32-0, has the systematic name of (3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[(3S)-3-(4-fluorophenyl)-3-hydroxypropyl]azetidin-2-one. It belongs to the following product categories: (intermediate of ezetimibe); Ezetimibe intermediates. And the molecular formula of the chemical is C31H27F2NO3.

The characteristics of this chemical are as followings: (1)ACD/LogP: 5.99; (2)# of Rule of 5 Violations: 1; (3)ACD/LogD (pH 5.5): 6; (4)ACD/LogD (pH 7.4): 6; (5)ACD/BCF (pH 5.5): 9945; (6)ACD/BCF (pH 7.4): 9945; (7)ACD/KOC (pH 5.5): 25298; (8)ACD/KOC (pH 7.4): 25298; (9)#H bond acceptors: 4; (10)#H bond donors: 1; (11)#Freely Rotating Bonds: 10; (12)Polar Surface Area: 49.77 Å2; (13)Index of Refraction: 1.617; (14)Molar Refractivity: 137.559 cm3; (15)Molar Volume: 393.064 cm3; (16)Polarizability: 54.533×10-24cm3; (17)Surface Tension: 51.27 dyne/cm; (18)Density: 1.271 g/cm3; (19)Flash Point: 381.055 °C; (20)Enthalpy of Vaporization: 108.517 kJ/mol; (21)Boiling Point: 706.462 °C at 760 mmHg; (22)Vapour Pressure: 0 mmHg at 25°C.

Addtionally, the following datas could be converted into the molecular structure:
(1)SMILES: Fc1ccc(cc1)[C@@H](O)CC[C@H]5C(=O)N(c2ccc(F)cc2)[C@@H]5c4ccc(OCc3ccccc3)cc4
(2)InChI: InChI=1/C31H27F2NO3/c32-24-10-6-22(7-11-24)29(35)19-18-28-30(34(31(28)36)26-14-12-25(33)13-15-26)23-8-16-27(17-9-23)37-20-21-4-2-1-3-5-21/h1-17,28-30,35H,18-20H2/t28-,29+,30-/m1/s1
(3)InChIKey: KEYVFYMGVLFXQK-DYIKCSJPBL

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