Methanamine, N-methoxy-, hydrochloride (1:1) → 2-Fluoro-N-methoxy-N-methylnicotinamide
Reaction equation
CN([C:4]([O:8][N:9]1N=NC2C=CC=C[C:10]1=2)=[N+](C)C)C.[B-](F)(F)(F)F.[F:23][C:24]1[N:32]=[CH:31][CH:30]=[CH:29][C:25]=1[C:26](O)=[O:27].Cl.CONC.C(N(C(C)C)CC)(C)C>ClCCl>[F:23][C:24]1[N:32]=[CH:31][CH:30]=[CH:29][C:25]=1[C:26]([N:9]([O:8][CH3:4])[CH3:10])=[O:27]Participants
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Procedure
TBTU coupling agent (13 g, 40 mmol) was added to a solution of 2-fluoronicotinic acid (5.6 g, 40 mmol), N-methoxy-N-methylamine hydrochloride (4.4 g, 45 mmol) and diisopropylethylamine (16 ml, 0.1 mol) in dichloromethane (100 ml) under nitrogen. The reaction mixture was stirred at room temperature for eighteen hours. It was diluted with more dichloromethane (200 ml), washed with a 2M aqueous hydrochloric acid solution (50 ml), a saturated sodium bicarbonate solution (100 ml), and brine (100 ml). The organic was dried over magnesium sulfate and, after filtration, concentrated in vacuo. The residue was purified by flash chromatography (120 g SiO2, pentane/ethyl acetate) to afford the title compound as a colourless oil (6 g, 80%). 1H NMR (CDCl3): 3.40-3.45 (3H, s), 3.55-3.65 (3H, s), 7.75-7.80 (1H, t), 7.90-7.95 (1H, t), 8.28-8.30 (1H, d).
Workup
- washwashed with a 2M aqueous hydrochloric acid solution (50 ml)
- dry with materialThe organic was dried over magnesium sulfate
- filtrationafter filtration
- concentrationconcentrated in vacuo
- customThe residue was purified by flash chromatography (120 g SiO2, pentane/ethyl acetate)
Sources & evidence
- ORD record
- ord-a280e983de3a4f7fb2ebff7e4d2f08af
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08741931B2
Reaction notes
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