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

HRID 1610473Notes

Reaction equation

HRID 1610473 reaction equation
[BH4-].[Na+].[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH:11]([C:17](=[O:28])[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:6][CH:5]=1.Cl>CCOCC.[Cl-].[Zn+2].[Cl-]>[F:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][CH:11]([CH:17]([OH:28])[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:6][CH:5]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 22261408Ethyl 2-((4-fluorophenyl)methyl)-3-oxo-3-(4-(trifluoromethyl)phenyl)propionate

Product 1

HCID 22261474ethyl(2RS,3RS)-2-((4-fluorophenyl)methyl)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propionateYield 100%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of zinc chloride (21.54 g, 158 mmol) in ether (500 ml) was added sodium borohydride (11.96 g, 316 mmol), and the mixture was stirred at room temperature for 30 min. Precipitated sodium chloride was filtered off. To the filtrate was gradually added a solution of ethyl 2-((4-fluorophenyl)methyl)-3-oxo-3-(4-(trifluoromethyl)phenyl)propionate (28 g, 79 mmol) in ether (200 ml) under ice-cooling, and the mixture was stirred at room temperature for 30 min. The reaction solution was poured into 1N aqueous hydrochloric acid solution (500 ml), and extracted with ethyl acetate (500 ml×2). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give ethyl(2RS,3RS)-2-((4-fluorophenyl)methyl)-3-hydroxy-3-(4-(trifluoromethyl)phenyl)propionate (28 g, 100%) as a colorless oil.

Workup

  1. filtrationPrecipitated sodium chloride was filtered off
  2. temperaturecooling
  3. stirringthe mixture was stirred at room temperature for 30 min
  4. extractionextracted with ethyl acetate (500 ml×2)
  5. washThe extract was washed with saturated brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. customevaporated under reduced pressure
  8. customThe residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-d2a9490ab25c4086a28fb5578a97f569
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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