Methanamine, N-methoxy-, hydrochloride (1:1) → N-methoxy-N-methyl-6-(trifluoromethyl)nicotinamide
Reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7](Cl)=[O:8])=[CH:5][N:4]=1.Cl.[CH3:15][NH:16][O:17][CH3:18].C(N(C(C)C)CC)(C)C>ClCCl>[CH3:18][O:17][N:16]([CH3:15])[C:7](=[O:8])[C:6]1[CH:10]=[CH:11][C:3]([C:2]([F:13])([F:12])[F:1])=[N:4][CH:5]=1Participants
Conditions
- Temperature
- 7 °C
Procedure
To a 1 L 3-neck flask equipped with an overhead stirrer, Claisen adaptor, nitrogen bubbler, 125 mL addition funnel, and thermocouple was added 6-(trifluoromethyl)nicotinoyl chloride (49.3 g, 235.2 mmol, Intermediate 36: step a), dichloromethane (493 mL), and N,O-dimethylhydroxylamine hydrochloride (25.63 g, 258.8 mmol). After the mixture was cooled to 7° C., diisopropylethylamine (90.263 mL, 517.6 mmol) was added such that the addition temperature did not exceed 16° C. After the addition, the reaction was allowed to warm to room temperature. The reaction was then transferred to a separatory funnel and the organic layer was washed with saturated aqueous NaHCO3 (2×100 mL) followed by water (100 mL) and then dried over sodium sulfate, then filtered. Solvent removal afforded the title compound as a brownish oil.
Workup
- customTo a 1 L 3-neck flask equipped with an overhead stirrer
- additionClaisen adaptor, nitrogen bubbler, 125 mL addition funnel
- customdid not exceed 16° C
- additionAfter the addition
- temperatureto warm to room temperature
- customThe reaction was then transferred to a separatory funnel
- washthe organic layer was washed with saturated aqueous NaHCO3 (2×100 mL)
- dry with materialdried over sodium sulfate
- filtrationfiltered
- customSolvent removal
Sources & evidence
- ORD record
- ord-94ed3c6d7157412998187672cbdade89
- Source dataset
- uspto-grants-2016_03
- Patent number
- US09290476B2
Reaction notes
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