Methanamine, N-methoxy-, hydrochloride (1:1) → 2-fluoro-N-methoxy-N,5-dimethylnicotinamide
Reaction equation
[F:1][C:2]1[N:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4](O)=[O:5].Cl.[CH3:13][NH:14][O:15][CH3:16].C(N(C(C)C)CC)(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.[B-](F)(F)(F)F>ClCCl>[F:1][C:2]1[N:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([N:14]([O:15][CH3:16])[CH3:13])=[O:5]Participants
6
Reactant 4
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
To a solution of 2-fluoro-5-methylnicotinic acid (4.9 g, 31.6 mmol), N,O-dimethylhydroxylamine hydrochloride (4.01 g, 41.08 mmol), diisopropylethylamine (12.6 ml, 72.68 mmol) in dichloromethane (150 ml) at 0° C. was added TBTU (11.16 g, 34.76 mmol) portionwise over 30 minutes. The solution was stirred at 0° C. for a further 10 minutes then, at room temperature for 18 hours. The reaction mixture was washed with a 10 wt % solution of citric acid and brine. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The residue was purified on silica gel by flash column chromatography (ISCO Companion□, 80 g column, 0-20% EtOAc/Petrol) to afford the title compound as a colourless solid (5.44 g, 87% yield).
Workup
- waitat room temperature for 18 hours
- washThe reaction mixture was washed with a 10 wt % solution of citric acid and brine
- dry with materialThe organic layer was dried over magnesium sulfate
- filtrationfiltered
- concentrationconcentrated in vacuo
- customThe residue was purified on silica gel by flash column chromatography (ISCO Companion□, 80 g column, 0-20% EtOAc/Petrol)
Sources & evidence
- ORD record
- ord-98f3f57728dc41e998429ab381b0500a
- Source dataset
- uspto-grants-2014_06
- Patent number
- US08741931B2
Reaction notes
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