Sodium borohydride → ethyl (2RS,3RS)-2-[3-(1,1-difluoroethyl)benzyl]-3-(4-fluorophenyl)-3-hydroxypropionate

HRID 1610723Notes

Reaction equation

HRID 1610723 reaction equation
[BH4-].[Na+].[F:3][C:4]([C:7]1[CH:8]=[C:9]([CH:26]=[CH:27][CH:28]=1)[CH2:10][CH:11]([C:17]([C:19]1[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=1)=[O:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])([F:6])[CH3:5]>CCOCC.[Cl-].[Zn+2].[Cl-]>[F:3][C:4]([C:7]1[CH:8]=[C:9]([CH:26]=[CH:27][CH:28]=1)[CH2:10][CH:11]([CH:17]([C:19]1[CH:20]=[CH:21][C:22]([F:25])=[CH:23][CH:24]=1)[OH:18])[C:12]([O:14][CH2:15][CH3:16])=[O:13])([F:6])[CH3:5]

Participants

5

Reactant 2

HCID 4311764Sodium borohydrideHCID 22261820Ethyl 2-[3-(1,1-difluoroethyl)benzyl]-3-(4-fluorophenyl)-3-oxopropionate

Product 1

HCID 86593306ethyl (2RS,3RS)-2-[3-(1,1-difluoroethyl)benzyl]-3-(4-fluorophenyl)-3-hydroxypropionateYield 87%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolvent2×

Procedure

To a suspension (40 ml) of zinc chloride (5.35 g, 39.2 mmol) in ether was added sodium borohydride (2.97 g, 78.4 mmol) at room temperature, and the mixture was stirred as it was for 2 hrs. Insoluble material was filtered off. To the filtrate was added a solution of ethyl 2-[3-(1,1-difluoroethyl)benzyl]-3-(4-fluorophenyl)-3-oxopropionate (7.16 g, 19.6 mmol) in ether (40 ml), and the mixture was stirred at room temperature for 1.5 hrs. The reaction was quenched with 1N hydrochloric acid, and the mixture was diluted with ethyl acetate and washed with water and saturated brine. The mixture was dried over anhydrous magnesium sulfate, filtered and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1, 4:1) to give ethyl (2RS,3RS)-2-[3-(1,1-difluoroethyl)benzyl]-3-(4-fluorophenyl)-3-hydroxypropionate (6.24 g, 87%) as a colorless transparent oil.

Workup

  1. filtrationInsoluble material was filtered off
  2. stirringthe mixture was stirred at room temperature for 1.5 hrs
  3. customThe reaction was quenched with 1N hydrochloric acid
  4. additionthe mixture was diluted with ethyl acetate
  5. washwashed with water and saturated brine
  6. dry with materialThe mixture was dried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=8:1, 4:1)

Sources & evidence

ORD record
ord-55ec6dcb952746c5aec907c30767b205
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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