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

Name
(3R,4S)-4-[4-(Benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one
EINECS 1308068-626-2
CAS No. 190595-65-4
Article Data28
CAS DataBase
Density 1.264 g/cm³
Solubility
Melting Point
Formula C₃₁H₂₅F₂NO₃
Boiling Point 706.794 °C at 760 mmHg
Molecular Weight 497.541
Flash Point 381.255 °C
Transport Information
Appearance WHITE
Safety
Risk Codes
Molecular Structure
Hazard Symbols
Synonyms Ezetimibe Intermediates
PSA 46.61000
LogP 6.97600

Synthetic route

: 954109-22-9
(3R,4S)-4-(4-benzyloxyphenyl)-1-(4-fluoro phenyl)-3-{2-[2-(4-fluorophenyl)-[1,3]-dioxolan-2-yl]ethyl}azetidin-2-one

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

Conditions

Conditions	Yield
With water; toluene-4-sulfonic acid In acetone at 20℃; for 6h; Product distribution / selectivity; Reflux;	99%

: (S)-ethyl 2-((4-(benzyloxy)phenyl)(4-fluorophenylamino)methyl)-5-(4-fluorophenyl)-5-oxopentanoate

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

Conditions

Conditions	Yield
at 20℃; for 0.166667h; Temperature;	91.6%

: 953805-24-8
(3R,4S)-4-(4-benzyloxyphenyl)-1-(4-fluorophenyl)-3-{2-[2-(4-fluorophenyl)-5,5-dimethyl-[1,3]dioxan-2-yl]-ethyl}azetidin-2-one

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

Conditions

Conditions	Yield
With formic acid In dichloromethane for 12h; Reflux;	90%
With sulfuric acid In water; isopropyl alcohol at 20 - 25℃; for 1h; Product distribution / selectivity;	87.9%
With acetic acid at 20 - 25℃; for 1h; Product distribution / selectivity;	85.3%

: 190595-64-3
(3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-((E)-3-(4-fluorophenyl)allyl)azetidin-2-one

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

Conditions

Conditions	Yield
With perchloric acid; palladium diacetate; p-benzoquinone In water; acetonitrile for 16h;	90%

: 942485-56-5
(S)-3-{4-[2-(4-fluorophenyl)dioxolan-2-yl]butanoyl}-4-phenyl-oxazolidin-2-one

: 70627-52-0
4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine

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

Conditions

Conditions	Yield
With N,O-bis-(trimethylsilyl)-acetamide; tetrabutyl ammonium fluoride In toluene at 60℃;	88.94%

: 1206694-77-0
(3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[(Z)-3-(4-fluorophenyl)allyl]azetidin-2-one

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

Conditions

Conditions	Yield
With perchloric acid; p-benzoquinone; palladium diacetate In water; acetonitrile for 48h; Inert atmosphere;	86%
With perchloric acid; water; palladium diacetate; p-benzoquinone In acetonitrile Wacker-Tsuji oxidation; Inert atmosphere;	86%

: C33H31F2NO4

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

Conditions

Conditions	Yield
With lithium hexamethyldisilazane In tetrahydrofuran at -20℃; for 0.666667h;	77%
With lithium hexamethyldisilazane In tetrahydrofuran at -20℃; for 0.666667h;	77%

: 934245-14-4
3-[(2S,3R)-2-(4-benzyloxyphenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]-N-methoxy-N-methylpropaneamide

: 352-13-6
4-flourophenylmagnesium bromide

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

Conditions

Conditions	Yield
In tetrahydrofuran; toluene at 30 - 32℃; for 2.5h; Solvent; Temperature;	75.7%

: 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

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

Conditions

Conditions	Yield
With Wilkinson's catalyst; hydrogen In dichloromethane under 3102.89 Torr; for 18h; Hydrogenation;	71%

: 352-13-6
4-flourophenylmagnesium bromide

: 204589-84-4
3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl)azetidin-3-yl)propionic acid chloride

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

Conditions

Conditions	Yield
Stage #1: 4-flourophenylmagnesium bromide With zinc(II) chloride In tetrahydrofuran at 4℃; Stage #2: 3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl)azetidin-3-yl)propionic acid chloride; tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 0℃; for 4.5h;	37%
With zinc(II) chloride; palladium diacetate In toluene at 0 - 20℃; for 2h;

: 181705-93-1
4-fluorophenylzinc bromide

: 204589-84-4
3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl)azetidin-3-yl)propionic acid chloride

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

Conditions

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 10℃; for 1h; Yield given;
palladium diacetate In toluene at 20℃; for 0.75h;
Stage #1: 4-fluorophenylzinc bromide; 3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl)azetidin-3-yl)propionic acid chloride; palladium diacetate In toluene at 10 - 11℃; for 0.333333h; Stage #2: With hydrogenchloride; water In toluene

: 70627-52-0
4-benzyloxybenzylidene-N-(4-fluoro)phenylanisidine

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

Conditions

Conditions	Yield
Multi-step reaction with 5 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 View Scheme
Multi-step reaction with 3 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 View Scheme

Yield

Multi-step reaction with 5 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
View Scheme

Multi-step reaction with 3 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
View Scheme

: 221349-58-2
(2S,3S)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxazetidine-3-carbaldehyde

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

Conditions

Conditions	Yield
Multi-step reaction with 3 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 View Scheme

: 221349-56-0
(3S,4S)-4-(4-Benzyloxy-phenyl)-3-((S)-1,2-dihydroxy-ethyl)-1-(4-fluoro-phenyl)-azetidin-2-one

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

Conditions

Conditions	Yield
Multi-step reaction with 4 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 View Scheme

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

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

Conditions

Conditions	Yield
Multi-step reaction with 3 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 View Scheme

: 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

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

Conditions

Conditions	Yield
Multi-step reaction with 2 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 View Scheme

: 219653-96-0
(Z)-1-(4-(benzyloxy)phenyl)-N-(4-fluorophenyl)methaneimine

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

Conditions

Conditions	Yield
Multi-step reaction with 4 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 View Scheme

: 204589-82-2
(3R,4S)-1-(4-fluorophenyl)-3-(3-hydroxy-3-oxopropyl)-4-(4-benzyloxyphenyl)-2-azetidinone

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

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: oxalyl chloride / CH2Cl2 / 16 h / 22 °C 2: (Ph3P)4Pd / tetrahydrofuran / 1 h / 10 °C View Scheme

: 204589-80-0
methyl 3-((2S,3R)-2-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl)propanoate

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

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: LiOH*H2O / methanol / 2 h 2: oxalyl chloride / CH2Cl2 / 16 h / 22 °C 3: (Ph3P)4Pd / tetrahydrofuran / 1 h / 10 °C View Scheme
Multi-step reaction with 2 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 View Scheme

: 460-00-4
1-Bromo-4-fluorobenzene

: 204589-84-4
3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl)azetidin-3-yl)propionic acid chloride

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

Conditions

Conditions	Yield
With magnesium; Iron acetylacetonate In tetrahydrofuran at -85 - -78℃; for 1.08333h; Purification / work up;
With iodine; magnesium; Iron acetylacetonate In tetrahydrofuran at -90 - -78℃; for 0.0333333h; Purification / work up;

: 133472-27-2
4-fluorophenylzinc chloride

: 204589-84-4
3-((3R,4S)-1-(4-fluorophenyl)-2-oxo-4-(4-(benzyloxy)phenyl)azetidin-3-yl)propionic acid chloride

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

Conditions

Conditions	Yield
tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 0 - 22℃; for 1.5h;

: 133472-27-2
4-fluorophenylzinc chloride

: 204589-82-2
(3R,4S)-1-(4-fluorophenyl)-3-(3-hydroxy-3-oxopropyl)-4-(4-benzyloxyphenyl)-2-azetidinone

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

Conditions

Conditions	Yield
Stage #1: (3R,4S)-1-(4-fluorophenyl)-3-(3-hydroxy-3-oxopropyl)-4-(4-benzyloxyphenyl)-2-azetidinone With oxalyl dichloride; N,N-dimethyl-formamide In dichloromethane at 20℃; Negishi coupling reaction; Stage #2: 4-fluorophenylzinc chloride With palladium diacetate In tetrahydrofuran; toluene at 10 - 11℃; for 0.333333h; Negishi coupling reaction;	127.5 g

: 231301-01-2
C31H23F2NO3

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

Conditions

Conditions	Yield
With hydrogen; Wilkinson's catalyst In dichloromethane under 3375.34 Torr; for 18h;

: 934245-14-4
3-[(2S,3R)-2-(4-benzyloxyphenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]-N-methoxy-N-methylpropaneamide

: 460-00-4
1-Bromo-4-fluorobenzene

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

Conditions

Conditions	Yield
Stage #1: 1-Bromo-4-fluorobenzene With magnesium In tetrahydrofuran at 40 - 45℃; for 1h; Heating / reflux; Stage #2: 3-[(2S,3R)-2-(4-benzyloxyphenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]-N-methoxy-N-methylpropaneamide In tetrahydrofuran at 0 - 10℃; for 0.75 - 0.833333h; Stage #3: With hydrogenchloride In tetrahydrofuran; water at 10 - 15℃;
Stage #1: 1-Bromo-4-fluorobenzene With magnesium In tetrahydrofuran at 40 - 50℃; for 1h; Inert atmosphere; Stage #2: 3-[(2S,3R)-2-(4-benzyloxyphenyl)-1-(4-fluorophenyl)-4-oxoazetidin-3-yl]-N-methoxy-N-methylpropaneamide In tetrahydrofuran at -5 - 0℃; for 1h;	34.5 g

: C32H28F2N2O3

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

Conditions

Conditions	Yield
With hydrogenchloride; water In 1,4-dioxane; acetone at 90 - 95℃; for 6h;

: 189028-93-1
(S)-1-(4-fluorophenyl)-5-(2-oxo-4-phenyloxazolidin-3-yl)pentane-1,5-dione

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

Conditions

Conditions	Yield
Multi-step reaction with 4 steps 1.1: hydroxylamine hydrochloride / pyridine / 0 - 20 °C 2.1: titanium(IV) isopropylate; N-ethyl-N,N-diisopropylamine; titanium tetrachloride / dichloromethane / 0 °C 2.2: -15 °C 3.1: N,O-bis-(trimethylsilyl)-acetamide / toluene / 0.5 h / 60 °C 3.2: 8 h / 60 °C 3.3: 20 h / 20 °C 4.1: hydrogenchloride; formaldehyd / water; tetrahydrofuran / 6 h / 20 °C View Scheme
Multi-step reaction with 5 steps 1.1: hydroxylamine hydrochloride / pyridine / 0 - 20 °C 2.1: dmap; 1H-imidazole / dichloromethane / 0.17 h / 20 °C 2.2: 5 h 3.1: titanium(IV) isopropylate; N-ethyl-N,N-diisopropylamine; titanium tetrachloride / dichloromethane / 0 °C 3.2: 3 h / -15 °C 4.1: N,O-bis-(trimethylsilyl)-acetamide / toluene / 0.5 h / 60 °C 4.2: 8 h / 60 °C 5.1: hydrogenchloride; formaldehyd / water; tetrahydrofuran / 4 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: phosphorus pentoxide; sulfuric acid / dichloromethane / 5 h / Reflux 2: N-ethyl-N,N-diisopropylamine; titanium(IV) isopropylate; titanium tetrachloride / dichloromethane / 3 h / -5 °C 3: N,O-Bis(trimethylsilyl)acetamide; tetrabutyl ammonium fluoride / toluene / 48 h / Reflux 4: formic acid / dichloromethane / 12 h / Reflux View Scheme
Multi-step reaction with 2 steps 1: toluene-4-sulfonic acid / hexane / 6 h / 25 °C 2: N,O-bis-(trimethylsilyl)-acetamide; tetrabutyl ammonium fluoride / toluene / 60 °C View Scheme

: (S)-3-(5-(4-fluorophenyl)-5-(hydroxyimino)pentanoyl)-4-phenyloxazolidin-2-one

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

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: titanium(IV) isopropylate; N-ethyl-N,N-diisopropylamine; titanium tetrachloride / dichloromethane / 0 °C 1.2: -15 °C 2.1: N,O-bis-(trimethylsilyl)-acetamide / toluene / 0.5 h / 60 °C 2.2: 8 h / 60 °C 2.3: 20 h / 20 °C 3.1: hydrogenchloride; formaldehyd / water; tetrahydrofuran / 6 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: dmap; 1H-imidazole / dichloromethane / 0.17 h / 20 °C 1.2: 5 h 2.1: titanium(IV) isopropylate; N-ethyl-N,N-diisopropylamine; titanium tetrachloride / dichloromethane / 0 °C 2.2: 3 h / -15 °C 3.1: N,O-bis-(trimethylsilyl)-acetamide / toluene / 0.5 h / 60 °C 3.2: 8 h / 60 °C 4.1: hydrogenchloride; formaldehyd / water; tetrahydrofuran / 4 h / 20 °C View Scheme

Yield

Multi-step reaction with 3 steps
1.1: titanium(IV) isopropylate; N-ethyl-N,N-diisopropylamine; titanium tetrachloride / dichloromethane / 0 °C
1.2: -15 °C
2.1: N,O-bis-(trimethylsilyl)-acetamide / toluene / 0.5 h / 60 °C
2.2: 8 h / 60 °C
2.3: 20 h / 20 °C
3.1: hydrogenchloride; formaldehyd / water; tetrahydrofuran / 6 h / 20 °C
View Scheme

Multi-step reaction with 4 steps
1.1: dmap; 1H-imidazole / dichloromethane / 0.17 h / 20 °C
1.2: 5 h
2.1: titanium(IV) isopropylate; N-ethyl-N,N-diisopropylamine; titanium tetrachloride / dichloromethane / 0 °C
2.2: 3 h / -15 °C
3.1: N,O-bis-(trimethylsilyl)-acetamide / toluene / 0.5 h / 60 °C
3.2: 8 h / 60 °C
4.1: hydrogenchloride; formaldehyd / water; tetrahydrofuran / 4 h / 20 °C
View Scheme

: 1380431-24-2
(3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-(4-fluorophenyl)-3-(hydroxyimino)propyl)azetidin-2-one

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

Conditions

Conditions	Yield
Stage #1: (3R,4S)-4-(4-(benzyloxy)phenyl)-1-(4-fluorophenyl)-3-(3-(4-fluorophenyl)-3-(hydroxyimino)propyl)azetidin-2-one With hydrogenchloride; formaldehyd In tetrahydrofuran; water at 20℃; for 6h; Stage #2: With sodium hydrogencarbonate In tetrahydrofuran; water; ethyl acetate

: 1380431-27-5
(3R,4S)-4-(4-(benzyloxy)phenyl)-3-(3-(tert-butyldimethylsilyloxyimino)-3-(4-fluorophenyl)propyl)-1-(4-fluorophenyl)azetidin-2-one

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

Conditions

Conditions	Yield
Stage #1: (3R,4S)-4-(4-(benzyloxy)phenyl)-3-(3-(tert-butyldimethylsilyloxyimino)-3-(4-fluorophenyl)propyl)-1-(4-fluorophenyl)azetidin-2-one With hydrogenchloride; formaldehyd In tetrahydrofuran; water at 20℃; for 4h; Stage #2: With sodium hydrogencarbonate In tetrahydrofuran; water; ethyl acetate Product distribution / selectivity;

: 1380431-20-8
(S)-3-(5-(tert-butyldimethylsilyloximino)-5-(4-fluorophenyl)pentanoyl)-4-phenyloxazolidin-2-one

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

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1.1: titanium(IV) isopropylate; N-ethyl-N,N-diisopropylamine; titanium tetrachloride / dichloromethane / 0 °C 1.2: 3 h / -15 °C 2.1: N,O-bis-(trimethylsilyl)-acetamide / toluene / 0.5 h / 60 °C 2.2: 8 h / 60 °C 3.1: hydrogenchloride; formaldehyd / water; tetrahydrofuran / 4 h / 20 °C View Scheme

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

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

Conditions

Conditions	Yield
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%

: 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(S)-hydroxy-3-(4-fluorophenyl)propyl]-[4-(phenylmethoxy)phenyl]-2-azetidinone

Conditions

Conditions	Yield
Stage #1: (3R,4S)-4-[4-(benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one With di-methylsulfide borane; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole In tetrahydrofuran at -10 - 20℃; for 2.5h; Inert atmosphere; Stage #2: With methanol In tetrahydrofuran for 0.5h; Inert atmosphere;	98.7%
With dimethylsulfide borane complex In dichloromethane

: 126-30-7
2,2-Dimethyl-1,3-propanediol

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

: 953805-24-8
(3R,4S)-4-(4-benzyloxyphenyl)-1-(4-fluorophenyl)-3-{2-[2-(4-fluorophenyl)-5,5-dimethyl-[1,3]dioxan-2-yl]-ethyl}azetidin-2-one

Conditions

Conditions	Yield
With Pyridine hydrobromide In toluene at 20 - 115℃; for 8h; Product distribution / selectivity;	77.1%
With pyridinium p-toluenesulfonate In toluene at 20 - 115℃; for 8h; Product distribution / selectivity;	72%
With toluene-4-sulfonic acid In toluene at 20 - 115℃; for 8h; Product distribution / selectivity;	70.4%

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

: 191330-56-0
[14C]-Sch 57871

Conditions

Conditions	Yield
With hydrogen; palladium on activated charcoal In ethanol under 3102.9 Torr; for 12h;
With hydrogen; palladium on activated charcoal In methanol under 2942.29 - 3310.08 Torr;

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

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

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

Conditions

Conditions	Yield
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;

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

: 163222-33-1
ezetemibe

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: 70 percent / CBS; BH3-Me2S / toluene; CH2Cl2 / 2 h / -20 °C 2: 79 percent / ammonium formate; HOAc / Pd-C / methanol / 3 h / 45 - 55 °C / pH 3 - 5 View Scheme
Multi-step reaction with 2 steps 1: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C 2: H2 / 10percent Pd/C / ethanol / 16 h / 3102.9 Torr View Scheme
Multi-step reaction with 2 steps 1: dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / dichloromethane; tetrahydrofuran / 5 h / 0 °C 2: palladium on activated charcoal; hydrogen / methanol / 6 h / 20 °C / 3800.26 Torr View Scheme
Multi-step reaction with 2 steps 1: dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; dichloromethane / 5 h / 0 °C 2: palladium on activated charcoal; hydrogen / methanol / 6 h / 20 °C / 3800.26 Torr View Scheme
Multi-step reaction with 2 steps 1: dimethylsulfide borane complex / tetrahydrofuran / 4 h / -10 °C / Inert atmosphere 2: palladium on activated charcoal; formic acid; ammonium formate / isopropyl alcohol / 3 h / 40 °C View Scheme

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

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

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: BH3Me2S / tetrahydrofuran / 3 h / 22 °C 2: H2 / 10percent Pd/C / ethanol / 16 h / 3102.9 Torr 3: p-TsOHH2O / toluene / 6 h / 80 °C View Scheme

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

: 163380-16-3
(3R,4S)-1-(4-fluorophenyl)-3-[(3R)-3-(4-fluorophenyl)-3-hydroxypropyl]-4-(4-hydroxyphenyl)-azetidin-2-one

Conditions

Conditions	Yield
Multi-step reaction with 2 steps 1: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C 2: H2 / 10percent Pd/C / ethanol / 16 h / 3102.9 Torr View Scheme

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

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

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C 2: H2 / 10percent Pd/C / ethanol / 16 h / 3102.9 Torr 3: 0.260 g / pyridine / CH2Cl2 / 1 h / 22 °C View Scheme

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

: 3(R)-[3(R)-(acetyloxy)-3-(4-fluorophenyl)propyl]-4(S)-[4-(acetyloxy)phenyl]-1-(4-fluorophenyl)-2-azetidinone

Conditions

Conditions	Yield
Multi-step reaction with 3 steps 1: BH3*Me2S / tetrahydrofuran / 3 h / 22 °C 2: H2 / 10percent Pd/C / ethanol / 16 h / 3102.9 Torr 3: pyridine / CH2Cl2 / 1 h / 22 °C View Scheme

: 67-56-1
methanol

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

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

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

Conditions

Conditions	Yield
With hydrogenchloride In tetrahydrofuran

...Expand

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

The (3R,4S)-4-[4-(Benzyloxy)phenyl]-1-(4-fluorophenyl)-3-[3-(4-fluorophenyl)-3-oxopropyl]azetidin-2-one , with the CAS register number 190595-65-4, has other names as E6:synthesis of trans-1-(4-fluorophenyl)-3-[3-oxo-3-(4-fluorophenyl)propyl .

The physical properties of this kind of chemical are as the following: (1)ACD/BCF (pH 5.5): 25455 ; (2)ACD/BCF (pH 7.4): 25455 ; (3)ACD/KOC (pH 5.5): 49573 ; (4)ACD/KOC (pH 7.4): 49573 ; (5)#H bond acceptors: 4 ; (6)#Freely Rotating Bonds: 9 ; (7)Polar Surface Area: 46.61 ; (8)Index of Refraction: 1.61 ; (9)Molar Refractivity: 136.5 cm³ ; (10)Molar Volume: 393.523 cm³ ; (11)Polarizability: 54.113×10^-24 cm³ ; (12)Surface Tension: 49.155 dyne/cm ; (13)Density: 1.264 g/cm³ ; (14)Flash Point: 381.255 °C ; (15)Enthalpy of Vaporization: 103.394 kJ/mol ; (16)Boiling Point: 706.794 °C at 760 mmHg.

This is a kind of white crystal and it is widely used in the pharmaceutic intermediates. And its product category are various, for example, the ezetimibe intermediates.

In addition, you could refer to the following data to get the molecular structure:
SMILES:c1ccc(cc1)COc2ccc(cc2)C3C(C(=O)N3c4ccc(cc4)F)CCC(=O)c5ccc(cc5)F
InChI:InChI=1/C31H25F2NO3/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/h1-17,28,30H,18-20H2/t28-,30-/m1/s1
InChIKey:BVYNXBNCXPJQCW-PQHLKRTFBD

As for its market information, there are many suppliers in China, such as Ningbo Hi-Tech Biochemicals Co., Ltd. and Yancheng Henz Chemical Co., Ltd.

Product Name

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

Synthetic route

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

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