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

HRID 333855Notes

Reaction equation

HRID 333855 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-c766c07af26048b493d656c7e5c96fb3
Source dataset
uspto-grants-2014_11
Patent number
US08883786B2

Reaction notes

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