Hydrochloric Acid → N-(2-(4-fluorophenyl)-2-hydroxy-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-oxo-4H-pyran-2-carboxamide

HRID 1610171Notes

Reaction equation

HRID 1610171 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:31])[CH:9]([NH:21][C:22]([C:24]2[O:25][CH:26]=[CH:27][C:28](=[O:30])[CH:29]=2)=[O:23])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)=[CH:4][CH:3]=1.[BH4-].[Na+].Cl>CO.[Cl-].[Mn+2].[Cl-]>[F:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]([OH:31])[CH:9]([NH:21][C:22]([C:24]2[O:25][CH:26]=[CH:27][C:28](=[O:30])[CH:29]=2)=[O:23])[CH2:10][C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:18])[F:19])=[CH:13][CH:12]=2)=[CH:6][CH:7]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 4311764Sodium borohydrideHCID 22261520N-(2-(4-fluorophenyl)-2-oxo-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-oxo-4H-pyran-2-carboxamide

Product 1

HCID 22262042N-(2-(4-fluorophenyl)-2-hydroxy-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-oxo-4H-pyran-2-carboxamideYield 35%

Reagents, catalysts & solvents 2

HCID 10313134Manganese(2+) dichlorideCatalystHCID 887MethanolSolvent

Procedure

To a solution of N-(2-(4-fluorophenyl)-2-oxo-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-oxo-4H-pyran-2-carboxamide (400 mg, 0.92 mmol) in methanol (30 ml) was added manganese (II) chloride (232 mg, 1.85 mmol), and the mixture was stirred at room temperature for 30 min. To the reaction solution was added sodium borohydride (70 mg, 1.85 mmol) under ice-cooling and the mixture was stirred for 1 hr. The reaction solution was poured into 1N hydrochloric acid (30 ml), and extracted with ethyl acetate (50 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). High polar fractions were collected and concentrated, and the obtained crude crystal was washed with hexane to give N-(2-(4-fluorophenyl)-2-hydroxy-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-oxo-4H-pyran-2-carboxamide((1RS,2SR) form: (1RS,2RS) form=3:2, 139 mg, 35%).

Workup

  1. temperaturecooling
  2. stirringthe mixture was stirred for 1 hr
  3. extractionextracted with ethyl acetate (50 ml×2)
  4. washThe extract was washed with water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customevaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate)
  8. customHigh polar fractions were collected
  9. concentrationconcentrated
  10. customthe obtained crude crystal
  11. washwas washed with hexane

Sources & evidence

ORD record
ord-97faabb3fed04c69b6eff0a1ad6c5c36
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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