1,1'-Carbonyldiimidazole → 5-Fluoro-N,2-dimethoxy-N-methylnicotinamide

To a solution of 5-fluoro-2-methoxynicotinic acid (1 g, 5.8 mmol) in tetrahydrofuran (10 mL) was added 1,1′-carbonyldiimidazole (1.4 g, 8.77 mmol, 1.5 eq.) portionwise over a 5 min period. The resulting solution was stirred at room temperature for 20 min before adding O,N-Dimethyl-hydroxylamine hydrochloride (0.63 g, 6.43 mmol, 1.1 eq.) and then stirred for a further 72 hr. The resulting mixture was then partitioned between ethyl acetate (30 mL) and 2M aqueous hydrochloric acid (30 mL). The organic phase was washed with 1M aqueous sodium hydrogen carbonate (30 mL), followed by brine (30 mL) and then dried over magnesium sulphate. The resulting mixture was filtered and concentrated under reduced pressure to produce the title compound as a colourless oil (0.53 g, 43%). 1H NMR (400 MHz, CDCl3): δ ppm 3.36 (br. s., 3H) 3.55 (br. s., 3H) 3.97 (s, 3H) 7.33-7.44 (m, 1H) 8.06 (d, J=2.73 Hz, 1H).

1. stirringstirred for a further 72 hr
2. customThe resulting mixture was then partitioned between ethyl acetate (30 mL) and 2M aqueous hydrochloric acid (30 mL)
3. washThe organic phase was washed with 1M aqueous sodium hydrogen carbonate (30 mL)
4. dry with materialdried over magnesium sulphate
5. filtrationThe resulting mixture was filtered
6. concentrationconcentrated under reduced pressure

ORD record

ord-e8f810b6d04d47c59bec9c610a5b78d1

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08916593B2