Methyl iodide → N-[4-chloro-2-methyl-3-(trifluoromethyl)phenyl]-2,2-dimethylpropanamide
Reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:13])([CH3:12])[CH3:11])=[CH:4][C:3]=1[C:15]([F:18])([F:17])[F:16].[CH2:19]([Li])CCC.IC>C1COCC1.O.CCOCC>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9](=[O:14])[C:10]([CH3:11])([CH3:12])[CH3:13])=[C:4]([CH3:19])[C:3]=1[C:15]([F:16])([F:17])[F:18]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 2.5 °C
Procedure
To a solution of compound 18A (2.29 g, 8.19 mmol) in anhydrous THF (25 mL) cooled to 0-5° C. was added a solution of 1.6 M n-butyllithium in hexanes (12.3 mL, 19.7 mmol) slowly, so that the reaction temperature was maintained below 5° C. The solution was stirred at 0-5° C. for 1.5 h. A solution of iodomethane (0.56 mL, 9.01 mmol) in petroleum ether (2 mL) was then added over 20 min while maintaining the temperature below 5° C. The suspension was stirred at 0-5° C. for 1 h and diluted with water and ether. The aqueous layer was extracted with ether and the combined organic layers washed with brine, dried (MgSO4), filtered and concentrated. The residue was chromatographed (silica gel), eluting with CH2Cl2 to afford the title compound (1.60 g, 67%). MS (ES) m/z 294 [M+1]+.
Workup
- temperatureso that the reaction temperature was maintained below 5° C
- temperaturewhile maintaining the temperature below 5° C
- stirringThe suspension was stirred at 0-5° C. for 1 h
- extractionThe aqueous layer was extracted with ether
- washthe combined organic layers washed with brine
- dry with materialdried (MgSO4)
- filtrationfiltered
- concentrationconcentrated
- customThe residue was chromatographed (silica gel)
- washeluting with CH2Cl2
Sources & evidence
- ORD record
- ord-dbd1348a9375478fb789dfbb824cf7b4
- Source dataset
- uspto-grants-2008_07
- Patent number
- US07405234B2
Reaction notes
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