102293-80-1

Basic information

• Product Name: Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-
• Synonyms: Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-;6-Bromoacetyl-2,2-dimethyl-4H-benzo[1,3]dioxine;2-BROMO-1-(2,2-DIMETHYL-4H-1,3-BENZODIOXIN-6-YL)ETHANONE;2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone
• CAS NO: 102293-80-1
• Molecular Formula: C₁₂H₁₃BrO₃
• Molecular Weight: 285.13382
• Mol File: 102293-80-1.mol
• Article Data: 17

Chemical Properties

• Boiling Point: 390.4±42.0 °C(Predicted)
• Appearance: /
• Density: 1.415±0.06 g/cm3(Predicted)
• CAS DataBase Reference: Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-(CAS DataBase Reference)
• NIST Chemistry Reference: Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-(102293-80-1)
• EPA Substance Registry System: Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-(102293-80-1)

Safety Data

• Hazardous Substances Data: 102293-80-1(Hazardous Substances Data)

Usage

General Description

Ethanone, 2-bromo-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)- is a chemical compound with the molecular formula C11H11BrO3. It is a derivative of benzodioxin, which is a group of chemical compounds with a fused benzene and dioxin ring structure. This specific compound contains a bromine atom and a ketone group, making it a bromoketone. It is used in organic synthesis and medicinal chemistry for the production of various pharmaceuticals and agrochemicals. It may also have potential applications in the development of new materials and as a research chemical for studying chemical reactions and mechanisms. Due to its chemical structure and properties, it is important to handle and use this compound with care and according to safety guidelines.

Synthetic route

2-Methoxypropene (116-11-0) + 2-bromo-1-[4-hydroxy-3-(hydroxymethyl)-phenyl]ethanone (62932-94-9) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane at 0℃; for 0.666667h;	100%
With resin-SO3H In dichloromethane
With toluene-4-sulfonic acid In tetrahydrofuran at -10 - 10℃; for 1h;

2,2-dimethoxy-propane (77-76-9) + 2-bromo-1-[4-hydroxy-3-(hydroxymethyl)-phenyl]ethanone (62932-94-9) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
With toluene-4-sulfonic acid In dichloromethane	99%
With toluene-4-sulfonic acid In dichloromethane at 20℃;	84%
In dichloromethane at 20℃; for 10h;	82%

1-(2,2-dimethyl-4H-benzo[d][1,3]dioxan-6-yl)ethanone (54030-34-1) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
With bromine In diethyl ether at 10 - 15℃; for 2.33333h;	81.03%
Stage #1: 1-(2,2-dimethyl-4H-benzo[d][1,3]dioxan-6-yl)ethanone With sodium hexamethyldisilazane In tetrahydrofuran at -78℃; for 1h; Stage #2: With chloro-trimethyl-silane In tetrahydrofuran at -78℃; for 0.5h; Stage #3: With bromine In tetrahydrofuran at -78℃; for 1h;	57%
Stage #1: 1-(2,2-dimethyl-4H-benzo[d][1,3]dioxan-6-yl)ethanone With sodium hexamethyldisilazane In tetrahydrofuran at -75 - -70℃; for 1h; Stage #2: With chloro-trimethyl-silane; bromine In tetrahydrofuran at -75 - -70℃;	55%

4'-acetoxy-3'-(acetoxymethyl)acetophenone (24085-06-1) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: polyvinylpyridinium bromide perbromide resin / CH2Cl2 2: 1N HBr / tetrahydrofuran / 75 °C 3: resin-SO3H / CH2Cl2 View Scheme

3'-acetoxymethyl-4'-acetoxy-2-bromoacetophenone (24085-07-2) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 1N HBr / tetrahydrofuran / 75 °C 2: resin-SO3H / CH2Cl2 View Scheme

4-Hydroxyacetophenone (99-93-4) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: resin-bound piperazinomethylpolystyrene / H2O; tetrahydrofuran 1.2: 14 percent / pTSA / toluene / 110 °C 2.1: polyvinylpyridinium bromide perbromide resin / CH2Cl2 3.1: 1N HBr / tetrahydrofuran / 75 °C 4.1: resin-SO3H / CH2Cl2 View Scheme

salicylaldehyde (90-02-8) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: aluminum (III) chloride / dichloromethane / 15 h / Reflux 2: sodium tetrahydroborate; acetic acid / 1 h / 10 °C 3: dichloromethane / 10 h / 20 °C View Scheme
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / dichloromethane / 0.5 h / 50 °C 1.2: 12 h / 40 °C 2.1: sodium tetrahydroborate; acetic acid / 0 - 20 °C / Inert atmosphere 3.1: toluene-4-sulfonic acid / dichloromethane / 20 °C View Scheme

5-(2-bromoacetyl)-2-hydroxybenzaldehyde (115787-50-3) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; acetic acid / 1 h / 10 °C 2: dichloromethane / 10 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sodium tetrahydroborate; acetic acid / 0 - 20 °C / Inert atmosphere 2: toluene-4-sulfonic acid / dichloromethane / 20 °C View Scheme

5-bromo-2-hydroxybenzyl alcohol (2316-64-5) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: acetone 2: n-butyllithium / tetrahydrofuran 3: sodium hexamethyldisilazane / tetrahydrofuran 4: bromine View Scheme
Multi-step reaction with 3 steps 1.1: aluminum (III) chloride / tetrahydrofuran / 1 h / 0 - 30 °C / Inert atmosphere 2.1: n-butyllithium / tetrahydrofuran / 1 h / -75 - -70 °C 2.2: -75 - -70 °C 3.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -75 - -70 °C 3.2: -75 - -70 °C View Scheme
Multi-step reaction with 3 steps 1.1: toluene-4-sulfonic acid / N,N-dimethyl-formamide / 20 °C 2.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 2.2: 4 h / -78 °C / Inert atmosphere 3.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 3.2: 1 h / -78 °C 3.3: 1 h / -78 °C View Scheme

6-bromo-2,2-dimethyl-4H-benzo[1,3]dioxine (52113-69-6) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: n-butyllithium / tetrahydrofuran 2: sodium hexamethyldisilazane / tetrahydrofuran 3: bromine View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / tetrahydrofuran / 1 h / -75 - -70 °C 1.2: -75 - -70 °C 2.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -75 - -70 °C 2.2: -75 - -70 °C View Scheme
Multi-step reaction with 2 steps 1.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 1.2: 4 h / -78 °C / Inert atmosphere 2.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 2.2: 1 h / -78 °C 2.3: 1 h / -78 °C View Scheme

C15H22O3Si → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
With bromine

5-bromosalicyclaldehyde (1761-61-1) → 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1)

Conditions	Yield
Multi-step reaction with 4 steps 1.1: sodium tetrahydroborate; ethanol / 5 h / 0 - 20 °C 2.1: toluene-4-sulfonic acid / N,N-dimethyl-formamide / 20 °C 3.1: n-butyllithium / hexane; tetrahydrofuran / 1 h / -78 °C / Inert atmosphere 3.2: 4 h / -78 °C / Inert atmosphere 4.1: sodium hexamethyldisilazane / tetrahydrofuran / 1 h / -78 °C 4.2: 1 h / -78 °C 4.3: 1 h / -78 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 2-azido-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)ethanone (384340-05-0)

Conditions	Yield
With sodium azide In N,N-dimethyl-formamide at 20 - 30℃; for 2h;	97%
With sodium azide In N,N-dimethyl-formamide at 20℃; for 2h;	95%
With sodium azide In N,N-dimethyl-formamide at 20℃; for 2h;	89%
With sodium azide In DMF (N,N-dimethyl-formamide) at 20℃; for 2h;
With sodium azide In DMF (N,N-dimethyl-formamide) at 20℃; for 2h;

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (R)-2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanol

Conditions	Yield
With sodium formate; η5-pentamethylcyclopentadienylrhodium dimer In water at 20℃; for 12h;	93%
With 2-(morpholin-4-yl)ethanol; β-nicotinamide adenine dinucleotide phosphate disodium salt; alcohol dehydrogenase CDX-005; nitric acid In water; dimethyl sulfoxide; isopropyl alcohol at 25℃; for 24h; Reagent/catalyst; Solvent; Large scale; Enzymatic reaction;	86.7%
With (1R,2S)-1-Amino-2-indanol; dimethyl sulfide borane In tetrahydrofuran at 20 - 25℃; for 3.5h;	76.12%

tert-butylamine (75-64-9) + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → C16H23NO3

Conditions	Yield
With potassium carbonate In tetrahydrofuran; water	93%

(2S)-2-phenylglycinol (20989-17-7) + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (1'S)-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-2-(2-hydroxy-1-phenyl-ethylamino)-ethanone (380414-67-5)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran for 4h;	80%
With resin-N(iPr)2 In tetrahydrofuran

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (R)-2-Bromo-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)ethanol (956234-46-1)

Conditions	Yield
Stage #1: 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone With sodium tetrahydroborate In methanol at 0℃; for 0.5h; Stage #2: With ammonium chloride In methanol; water at 0℃;	79%
With sodium tetrahydroborate In methanol at 0 - 20℃; for 1h;

C27H35N3O3 + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 2-(4-(benzyl(2-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-oxoethyl)amino)butyl)-4-(3,4-dimethoxyphenyl)-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 12h;	71%

C28H37N3O3 + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 2-(5-(benzyl(2-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-oxoethyl)amino)pentyl)-4-(3,4-dimethoxyphenyl)-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 12h;	70%

C29H39N3O3 + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 2-(6-(benzyl(2-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-oxoethyl)amino)hexyl)-4-(3,4-dimethoxyphenyl)-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 12h;	68%

C25H31N3O3 + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → cis-2-(3-(benzyl(2-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-oxoethyl)amino)propyl)-4-(3,4-dimethoxyphenyl)-4a,5,6,7,8,8a-hexahydrophthalazin-1(2H)-one

Conditions	Yield
With triethylamine In dichloromethane at 20℃; for 12h;	65%

(S)-2-methoxy-1-phenylethylamine (91298-74-7) + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-[(1S)-2-methoxy-1-phenylethylamino]ethanone (500317-68-0)

Conditions	Yield
With polystyryldiisopropylethylamine In tetrahydrofuran for 2h;	64%

iminodicarboxylic acid di-tert-butyl ester (51779-32-9) + 2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → di-(tert-butyl) 2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethyliminodicarbonate (452339-70-7)

Conditions	Yield
With caesium carbonate In acetonitrile at 20 - 25℃; for 6h; Inert atmosphere;	64%
With caesium carbonate In acetonitrile at 21℃; for 24h;	28%
With caesium carbonate In acetonitrile at 21℃; for 24h;

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (R)-(-)-salmeterol

Conditions	Yield
Multi-step reaction with 7 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C 3: 99 percent / (R)-tetrahydro-1-Me-3,3-Ph2-1H,3H-pyrrolo[1,2-c][1,3-2]oxaza; borole; BH3*THF / toluene / 5 - 20 °C 4: 70 percent / NaH / dimethylformamide / 3 h / 20 °C 5: 77 percent / NaH / dimethylformamide / 4 h / 5 - 20 °C 6: 96 percent / KOSiMe3 / tetrahydrofuran / 1 h / Heating 7: 80 percent / AcOH; MeOH / 72 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1.1: resin-N(iPr)2 / tetrahydrofuran 2.1: CaCl2 / methanol / 0.17 h / 0 °C 2.2: 76 percent / resin-NMe3(1+)*BH4(1-) / methanol / 2 h / 0 - 20 °C 3.1: (polystyrylmethyl)trimethylammonium cyanoborohydride; AcOH / CH2Cl2 3.2: 98 percent / resin-NMe3(1+)*NaCO3(1-) / CH2Cl2 4.1: H2 / Pd(OH)2/C / ethyl acetate / 2 h 4.2: 87 percent / SCX-2 View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (R)-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-(6-(4-phenylbutoxy)hexylamino)ethanol (590410-69-8)

Conditions	Yield
Multi-step reaction with 6 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C 3: 99 percent / (R)-tetrahydro-1-Me-3,3-Ph2-1H,3H-pyrrolo[1,2-c][1,3-2]oxaza; borole; BH3*THF / toluene / 5 - 20 °C 4: 70 percent / NaH / dimethylformamide / 3 h / 20 °C 5: 77 percent / NaH / dimethylformamide / 4 h / 5 - 20 °C 6: 96 percent / KOSiMe3 / tetrahydrofuran / 1 h / Heating View Scheme
Multi-step reaction with 4 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: 76 percent / CaCl2*2H2O; NaBH4 / methanol / 2 h / 0 °C 3: 87 percent / sodium triacetoxyborohydride / CH2Cl2 / 18 h 4: 87 percent / H2 / aq. Pd(OH)2/C / ethanol / 18 h View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (5R)-5-(2,2-dimethyl- 4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one (452339-73-0)

Conditions	Yield
Multi-step reaction with 4 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C 3: 99 percent / (R)-tetrahydro-1-Me-3,3-Ph2-1H,3H-pyrrolo[1,2-c][1,3-2]oxaza; borole; BH3*THF / toluene / 5 - 20 °C 4: 70 percent / NaH / dimethylformamide / 3 h / 20 °C View Scheme
Multi-step reaction with 4 steps 1: caesium carbonate / acetonitrile / 6 h / 20 - 25 °C / Inert atmosphere 2: trifluoroacetic acid / dichloromethane / 5 h / 10 - 25 °C 3: dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 1 h / -10 °C 4: potassium tert-butylate / N,N-dimethyl-formamide / 1 h / 10 - 20 °C View Scheme
Multi-step reaction with 4 steps 1: caesium carbonate / acetonitrile / 20 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 10 °C 3: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole; dimethylsulfide borane complex / toluene; tetrahydrofuran / 0.67 h / -10 °C / Inert atmosphere 4: potassium tert-butylate / N,N-dimethyl-formamide / 3 h / 0 - 20 °C / Inert atmosphere View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → tert-butyl 2-(2,2-dimethyl-4H-1,3-benzodioxane-6-yl)-2-carbonylethylcarbamate (452339-71-8)

Conditions	Yield
Multi-step reaction with 2 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C View Scheme
Multi-step reaction with 2 steps 1: caesium carbonate / acetonitrile / 6 h / 20 - 25 °C / Inert atmosphere 2: trifluoroacetic acid / dichloromethane / 5 h / 10 - 25 °C View Scheme
Multi-step reaction with 2 steps 1: caesium carbonate / acetonitrile / 20 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 10 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → tert-butyl (2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethylcarbamate (452339-72-9)

Conditions	Yield
Multi-step reaction with 3 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C 3: 99 percent / (R)-tetrahydro-1-Me-3,3-Ph2-1H,3H-pyrrolo[1,2-c][1,3-2]oxaza; borole; BH3*THF / toluene / 5 - 20 °C View Scheme
Multi-step reaction with 3 steps 1: caesium carbonate / acetonitrile / 6 h / 20 - 25 °C / Inert atmosphere 2: trifluoroacetic acid / dichloromethane / 5 h / 10 - 25 °C 3: dimethylsulfide borane complex; (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole / tetrahydrofuran; toluene / 1 h / -10 °C View Scheme
Multi-step reaction with 3 steps 1: caesium carbonate / acetonitrile / 20 °C 2: trifluoroacetic acid / dichloromethane / 2 h / 10 °C 3: (3aR)-1-methyl-3,3-diphenyl-tetrahydro-pyrrolo[1,2-c][1,3,2]oxazaborole; dimethylsulfide borane complex / toluene; tetrahydrofuran / 0.67 h / -10 °C / Inert atmosphere View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-[6-(4-phenylbutoxy)hexyl]-1,3-oxazolidin-2-one (590410-68-7)

Conditions	Yield
Multi-step reaction with 5 steps 1: 28 percent / Cs2CO3 / acetonitrile / 24 h / 21 °C 2: 43 percent / CF3CO2H / CH2Cl2 / 4 h / 20 °C 3: 99 percent / (R)-tetrahydro-1-Me-3,3-Ph2-1H,3H-pyrrolo[1,2-c][1,3-2]oxaza; borole; BH3*THF / toluene / 5 - 20 °C 4: 70 percent / NaH / dimethylformamide / 3 h / 20 °C 5: 77 percent / NaH / dimethylformamide / 4 h / 5 - 20 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-[(1S)-2-methoxy-1-phenylethylamino]ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: 64 percent / polystyryldiisopropylethylamine / tetrahydrofuran / 2 h 2: 91 percent / CaCl2; polystyryl(trimethyl)ammonium borohydride / methanol / 2 h / 0 - 20 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (1S)-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-[(1S)-2-hydroxy-1-phenylethylamino]ethanol

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: CaCl2*2H2O; NaBH4 / methanol / 2 h / 0 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (1R,1'S)-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-2-(2-hydroxy-1-phenyl-ethylamino)-ethanol (380414-68-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: 76 percent / CaCl2*2H2O; NaBH4 / methanol / 2 h / 0 °C View Scheme
Multi-step reaction with 2 steps 1.1: resin-N(iPr)2 / tetrahydrofuran 2.1: CaCl2 / methanol / 0.17 h / 0 °C 2.2: 76 percent / resin-NMe3(1+)*BH4(1-) / methanol / 2 h / 0 - 20 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (4S)-3-[2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethyl]-4-phenyl-1,3-oxazolidin-2-one

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: 91 percent / CH2Cl2 / 0.25 h 3: 87 percent / CaCl2; polystyryl(trimethyl)ammonium borohydride / methanol / 2 h / 0 - 20 °C View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (4S)-3-[2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethyl]-4-phenyl-1,3-oxazolidin-2-one (500317-72-6)

Conditions	Yield
Multi-step reaction with 2 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: 91 percent / CH2Cl2 / 0.25 h View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → (1R,1'S)-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-2-{(2-hydroxy-1-phenyl-ethyl)-[6-(4-phenyl-butoxy)-hexyl]-amino}-ethanol (380414-69-7)

Conditions	Yield
Multi-step reaction with 3 steps 1: 80 percent / i-Pr2NEt / tetrahydrofuran / 4 h 2: 76 percent / CaCl2*2H2O; NaBH4 / methanol / 2 h / 0 °C 3: 87 percent / sodium triacetoxyborohydride / CH2Cl2 / 18 h View Scheme
Multi-step reaction with 3 steps 1.1: resin-N(iPr)2 / tetrahydrofuran 2.1: CaCl2 / methanol / 0.17 h / 0 °C 2.2: 76 percent / resin-NMe3(1+)*BH4(1-) / methanol / 2 h / 0 - 20 °C 3.1: (polystyrylmethyl)trimethylammonium cyanoborohydride; AcOH / CH2Cl2 3.2: 98 percent / resin-NMe3(1+)*NaCO3(1-) / CH2Cl2 View Scheme

2-bromo-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)ethanone (102293-80-1) → 2-{bis-[6-(4-phenyl-butoxy)-hexyl]-amino}-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-ethanol

Conditions	Yield
Multi-step reaction with 3 steps 1.1: resin-N(iPr)2 / tetrahydrofuran 2.1: CaCl2 / methanol / 0.17 h / 0 °C 2.2: 76 percent / resin-NMe3(1+)*BH4(1-) / methanol / 2 h / 0 - 20 °C 3.1: H2 / Pd(OH)2/C / ethyl acetate View Scheme

Upstream product

• 116-11-0 2-Methoxypropene 
• 62932-94-9 2-bromo-1-[4-hydroxy-3-(hydroxymethyl)-phenyl]ethanone 
• 24085-06-1 4'-acetoxy-3'-(acetoxymethyl)acetophenone 
• 24085-07-2 3'-acetoxymethyl-4'-acetoxy-2-bromoacetophenone 
• 99-93-4 4-Hydroxyacetophenone 
• 54030-34-1 1-(2,2-dimethyl-4H-benzo[d][1,3]dioxan-6-yl)ethanone 
• 77-76-9 2,2-dimethoxy-propane 
• 90-02-8 salicylaldehyde 
• 115787-50-3 5-(2-bromoacetyl)-2-hydroxybenzaldehyde 
• 2316-64-5 5-bromo-2-hydroxybenzyl alcohol 
• 52113-69-6 6-bromo-2,2-dimethyl-4H-benzo[1,3]dioxine 
• 1761-61-1 5-bromosalicyclaldehyde 

Downstream Products

• 380414-67-5 (1'S)-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-2-(2-hydroxy-1-phenyl-ethylamino)-ethanone 
• 500317-68-0 1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-[(1S)-2-methoxy-1-phenylethylamino]ethanone 
• 452339-70-7 di-(tert-butyl) 2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethyliminodicarbonate 
• 135271-47-5 (R)-(-)-salmeterol 
• 590410-69-8 (R)-1-(2,2-dimethyl-4H-benzo[d][1,3]dioxin-6-yl)-2-(6-(4-phenylbutoxy)hexylamino)ethanol 
• 452339-73-0 (5R)-5-(2,2-dimethyl- 4H-1,3-benzodioxin-6-yl)-1,3-oxazolidin-2-one 
• 452339-71-8 tert-butyl 2-(2,2-dimethyl-4H-1,3-benzodioxane-6-yl)-2-carbonylethylcarbamate 
• 452339-72-9 tert-butyl (2R)-2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-hydroxyethylcarbamate 
• 590410-68-7 (5R)-5-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-3-[6-(4-phenylbutoxy)hexyl]-1,3-oxazolidin-2-one 
• 380414-68-6 (1R,1'S)-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-2-(2-hydroxy-1-phenyl-ethylamino)-ethanol 
• 500317-72-6 (4S)-3-[2-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-oxoethyl]-4-phenyl-1,3-oxazolidin-2-one 
• 380414-69-7 (1R,1'S)-1-(2,2-dimethyl-4H-benzo[1,3]dioxin-6-yl)-2-{(2-hydroxy-1-phenyl-ethyl)-[6-(4-phenyl-butoxy)-hexyl]-amino}-ethanol 
• 384340-08-3 (1S)-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl)-2-{[6-(4-phenylbutoxy)hexyl]amino}ethanol 
• 530118-35-5 C₃₅H₃₆BrNO₅ 

Relevant articles and documents

A convenient synthesis of (R)-salmeterol via Rh-catalyzed asymmetric transfer hydrogenation

(R)-Salmeterol was synthesized in eight steps with salicaldehyde as the starting material. The key chiral intermediate, alcohol 5, was prepared via Rh-catalyzed asymmetric transfer hydrogenation with (S,S)-PEG-BsDPEN or (S,S)-TsDPEN ligand and sodium formate as the hydrogen donor under mild conditions.

Levalbuterol intermediate and synthetic method of levalbuterol hydrochloride

The invention provides a levalbuterol intermediate and a levalbuterol hydrochloride synthesis method, and relates to a levalbuterol intermediate and a method for preparing levalbuterol hydrochloride from the intermediate. The method comprises steps as follows: 2-halogenate-1-(2,2-dimelthyl-4-hydrogen-benzo [d][1,3] dioxane)-butanone and organic amine have a Hoffman alkylation reaction to prepare a compound in the formula 2, the structural formula of the compound is shown in the specification, and the compound in the formula 2 is subjected to a reduction reaction, optically pure organic acid resolution and deprotection by hydrochloric acid to obtain levalbuterol hydrochloride. The method does not need processes of protection or deprotection and the like of hydroxyl groups on a benzene ring, protection, deprotection and purification processes are reduced, the synthesis route is short, operation is simple, meanwhile, borane-thioether does not need to be used as a reduction agent, and safety and environmental protection are realized.

METHOD OF PREPARING INTERMEDIATE OF SALMETEROL

A method of preparing an intermediate of salmeterol (Compound 1, 2-amino-1-(2,2-dimethyl-4H-1,3-benzodioxin-6-yl) ethanol) includes: reacting compound 2 with 2-methoxypropene in a first organic solvent to produce a reaction solution including compound 3, compound 2 including a 2-bromo precursor of Compound 1; reacting compound 3 with a nitrogen source to produce compound 4; reacting compound 4 with sodium borohydride in a second organic solvent to produce compound 5; and debenzylating compound 5 by ammonium formate / palladium-carbon catalytic transfer hydrogenation in a third organic solvent to produce Compound 1. A method of preparing salmeterol includes preparing Compound 1, and reacting Compound 1 to prepare salmeterol.