Methyl iodide → 5-[2-(2-Chloro-4-methoxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1-methyl-1H-pyridin-2-one

HRID 1097958Notes

Reaction equation

HRID 1097958 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:24])[C:11]([C:17]1[CH:18]=[CH:19][C:20](=[O:23])[NH:21][CH:22]=1)([OH:16])[C:12]([F:15])([F:14])[F:13].[C:25]([O-])([O-])=O.[K+].[K+].IC.CCOC(C)=O>CN(C)C(=O)C.O>[Cl:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH:10]([CH3:24])[C:11]([C:17]1[CH:18]=[CH:19][C:20](=[O:23])[N:21]([CH3:25])[CH:22]=1)([OH:16])[C:12]([F:14])([F:15])[F:13]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 574213125-[2-(2-Chloro-4-methoxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1H-pyridin-2-one

Product 1

HCID 574213135-[2-(2-Chloro-4-methoxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1-methyl-1H-pyridin-2-oneYield 108.8%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 31374DimethylacetamideSolvent

Procedure

To a solution of 5-[2-(2-chloro-4-methoxy-phenyl)-1-hydroxy-1-trifluoromethyl-propyl]-1H-pyridin-2-one (Example 194, 100 mg) in N,N-dimethylacetamide (1.5 ml) were added powdered K2CO3 (42 mg) and iodomethane (41 mg). The mixture was stirred at room temperature for 3 days. EtOAc and water were added and the mixture was extracted with EtOAc. The organic phase was dried (MgSO4), filtered and concentrated to dryness. The product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:1=>0:1) to give the title compound (113 mg, contains 10.7 mass-% of N,N-dimethylacetamide) as a light yellow oil. MS (m/e)=376.1 [M+H+].

Workup

  1. extractionthe mixture was extracted with EtOAc
  2. dry with materialThe organic phase was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated to dryness
  5. customThe product was purified by chromatography (SiO2, cyclohexane/EtOAc 1:1=>0:1)

Sources & evidence

ORD record
ord-1c2f75cc02814ae2849028d0b8de5801
Source dataset
uspto-grants-2012_03
Patent number
US08143280B2

Reaction notes

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