4-Phenylbutyric Acid → N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-phenylbutyramide

HRID 1610196Notes

Reaction equation

HRID 1610196 reaction equation
[C:1]1([CH2:7][CH2:8][CH2:9][C:10]([OH:12])=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(Cl)(=O)C(Cl)=O.Cl.[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27]([OH:41])[CH:28]([NH2:40])[CH2:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=2)=[CH:23][CH:22]=1.C(=O)([O-])O.[Na+]>O1CCCC1.C(OCC)(=O)C.O.CN(C)C=O>[F:20][C:21]1[CH:22]=[CH:23][C:24]([CH:27]([OH:41])[CH:28]([NH:40][C:10](=[O:12])[CH2:9][CH2:8][CH2:7][C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[CH2:29][C:30]2[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=2)=[CH:25][CH:26]=1

Participants

9

Reactant 4

HCID 47754-Phenylbutyric AcidHCID 65578Oxalyl chlorideHCID 516892Sodium BicarbonateHCID 22261728(1RS,2RS)-1-(4-fluorophenyl)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)-2-propylamine hydrochloride

Product 1

HCID 22261433N-((1RS,2SR)-2-(4-fluorophenyl)-2-hydroxy-1-((4-(trifluoromethyl)phenyl)methyl)ethyl)-4-phenylbutyramideYield 68.3%

Reagents, catalysts & solvents 4

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-phenylbutyric acid (141 mg, 0.86 mmol) in tetrahydrofuran (5 ml) were added oxalyl chloride (0.15 ml, 1.72 mmol) and N,N-dimethylformamide (0.01 ml), and the mixture was stirred at room temperature for 30 min. The reaction solution was evaporated under reduced pressure. To a solution of the residue in ethyl acetate (5 ml) were added (1RS,2SR)-1-(4-fluorophenyl)-1-hydroxy-3-(4-(trifluoromethyl)phenyl)-2-propylamine hydrochloride (200 mg, 0.57 mmol) and saturated aqueous sodium hydrogen carbonate (5 ml), and the mixture was stirred overnight at room temperature. The reaction solution was diluted with water (50 ml) and extracted with ethyl acetate (50 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=4:1-1:1) and recrystallized from ethyl acetate-hexane to give the title compound (179 mg, 68%).

Workup

  1. customThe reaction solution was evaporated under reduced pressure
  2. stirringthe mixture was stirred overnight at room temperature
  3. extractionextracted with ethyl acetate (50 ml×2)
  4. washThe extract was washed with 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 (hexane:ethyl acetate=4:1-1:1)
  8. customrecrystallized from ethyl acetate-hexane

Sources & evidence

ORD record
ord-f62334243408488c9d82be55a0b6cd82
Source dataset
uspto-grants-2006_01
Patent number
US06982348B2

Reaction notes

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