Hydrochloric Acid → ethyl (2RS,3RS)-3-(3-fluorophenyl)-3-hydroxy-2-((4-(trifluoromethyl)phenyl)methyl)propionate

HRID 1610369Notes

Reaction equation

HRID 1610369 reaction equation
[BH4-].[Na+].[F:3][C:4]1[CH:5]=[C:6]([C:10](=[O:28])[CH:11]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=2)[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:7]=[CH:8][CH:9]=1.Cl>C(OCC)C.[Cl-].[Zn+2].[Cl-]>[F:3][C:4]1[CH:5]=[C:6]([CH:10]([OH:28])[CH:11]([CH2:17][C:18]2[CH:19]=[CH:20][C:21]([C:24]([F:26])([F:27])[F:25])=[CH:22][CH:23]=2)[C:12]([O:14][CH2:15][CH3:16])=[O:13])[CH:7]=[CH:8][CH:9]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 22261560Ethyl 3-(3-fluorophenyl)-3-oxo-2-((4-(trifluoromethyl)phenyl)methyl)propionate

Product 1

HCID 86593241ethyl (2RS,3RS)-3-(3-fluorophenyl)-3-hydroxy-2-((4-(trifluoromethyl)phenyl)methyl)propionateYield 96.5%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of zinc chloride (14.8 g, 108.6 mmol) in diethyl ether (150 ml) was added sodium borohydride (8.22 g, 217 mmol) and the mixture was stirred at room temperature for 30 min. The insoluble material was filtered off. To the filtrate was added a solution of ethyl 3-(3-fluorophenyl)-3-oxo-2-((4-(trifluoromethyl)phenyl)methyl)propionate (20 g, 54.3 mmol) in diethyl ether (50 ml), and the mixture was stirred at room temperature for 30 min. 1N Hydrochloric acid was added to the reaction-solution under ice-cooling for quenching, water (200 ml) was added, and the mixture was extracted with ethyl acetate (300 ml×2). The extract was washed with water and saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-1:1) to give ethyl (2RS,3RS)-3-(3-fluorophenyl)-3-hydroxy-2-((4-(trifluoromethyl)phenyl)methyl)propionate (19.4 g, 96%) as a colorless oil.

Workup

  1. filtrationThe insoluble material was filtered off
  2. stirringthe mixture was stirred at room temperature for 30 min
  3. temperaturecooling
  4. customfor quenching
  5. additionwater (200 ml) was added
  6. extractionthe mixture was extracted with ethyl acetate (300 ml×2)
  7. washThe extract was washed with water and saturated brine
  8. dry with materialdried over anhydrous magnesium sulfate
  9. customevaporated under reduced pressure
  10. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=2:1-1:1)

Sources & evidence

ORD record
ord-ebc13ee847864169a4b211f08a554d7b
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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