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

HRID 1610431Notes

Reaction equation

HRID 1610431 reaction equation
[BH4-].[Na+].[O:3]=[C:4]([C:22]1[CH:27]=[CH:26][N:25]=[CH:24][CH:23]=1)[CH:5]([CH2:11][C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[CH:14][CH:13]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7].Cl.C(=O)([O-])O.[Na+]>C(OCC)C.[Cl-].[Zn+2].[Cl-]>[OH:3][CH:4]([C:22]1[CH:23]=[CH:24][N:25]=[CH:26][CH:27]=1)[CH:5]([CH2:11][C:12]1[CH:13]=[CH:14][C:15]([C:18]([F:19])([F:20])[F:21])=[CH:16][CH:17]=1)[C:6]([O:8][CH2:9][CH3:10])=[O:7]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 516892Sodium BicarbonateHCID 4311764Sodium borohydrideHCID 22262247Ethyl 3-oxo-3-(4-pyridyl)-2-((4-(trifluoromethyl)phenyl)methyl)propionate

Product 1

HCID 86593248ethyl (2RS,3RS)-3-hydroxy-3-(4-pyridyl)-2-((4-(trifluoromethyl)phenyl)methyl)propionateYield 90.1%

Reagents, catalysts & solvents 2

HCID 3007855ZincchlorideCatalystHCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of zinc chloride (8.14 g, 59.8 mmol) in diethyl ether (200 ml) was added sodium borohydride (4.53 g, 120 mmol), and the-mixture was stirred at room temperature for 30 min. The insoluble material was filtered off, and to the filtrate was added ethyl 3-oxo-3-(4-pyridyl)-2-((4-(trifluoromethyl)phenyl)methyl)propionate (10.5 g, 29.9 mmol) in diethyl ether (50 ml). The mixture was stirred at room temperature for 30 min. and 1N hydrochloric acid was added to the reaction solution under ice-cooling to quench the reaction. Saturated aqueous sodium hydrogen carbonate was added until the pH became 8, 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 (ethyl acetate) and recrystallized from diisopropyl ether-hexane to give ethyl (2RS,3RS)-3-hydroxy-3-(4-pyridyl)-2-((4-(trifluoromethyl)phenyl)methyl)propionate (9.52 g, 90%).

Workup

  1. filtrationThe insoluble material was filtered off
  2. stirringThe mixture was stirred at room temperature for 30 min.
  3. temperaturecooling
  4. customto quench
  5. customthe reaction
  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 (ethyl acetate)
  11. customrecrystallized from diisopropyl ether-hexane

Sources & evidence

ORD record
ord-8d1252f2bd6c47d2b4e538ef4b00701a
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

Loading…