2-Fluoro-N-methoxy-N-methylbenzamide

6638-79-5

393-52-2

198967-24-7

The general procedure for the synthesis of 2-fluoro-N-methoxy-N-methylbenzamide from dimethylhydroxylamine hydrochloride and o-fluorobenzoyl chloride was as follows: N,O-dimethylhydroxylamine hydrochloride (23.4 g, 240 mmol) was suspended in tetrahydrofuran (THF, 100 mL) and cooled to 0 °C under nitrogen protection. Pyridine (32 mL, 400 mmol) was added rapidly. A solution of o-fluorobenzoyl chloride (9.5 mL, 80 mmol) in THF (50 mL) was added dropwise over 15 minutes. The ice bath was removed and the reaction mixture was stirred at room temperature for 2 hours. Upon completion of the reaction, water (100 mL) and ethyl acetate (AcOEt, 100 mL) were added to separate the organic and aqueous phases. The aqueous phase was extracted again with ethyl acetate (100 mL). All organic phases were combined and washed sequentially with 1N hydrochloric acid (2 x 100 mL) and 1N sodium hydroxide (100 mL). The organic phase was dried with magnesium sulfate (MgSO4) and concentrated to give a yellow oil (10.7 g). The oily substance was purified by vacuum distillation and the colorless oily 2-fluoro-N-methoxy-N-methylbenzamide (9.1 g, 62% yield) distilled at 0.22 Torr, 57-59 °C was collected. The product was characterized by 1H-NMR (300 MHz, CDCl3): δ 3.34 (s, 3H), 3.54 (br, 3H), 7.10 (m, 1H), 7.19 (m, 1H), 7.42 (m, 2H).