863604-64-2

403-21-4

6638-79-5

863604-64-2

General procedure for the synthesis of 3-fluoro-N-methoxy-N-methyl-4-nitrobenzamide from 3-fluoro-4-nitrobenzoic acid and N-methoxymethylamine hydrochloride: 3-fluoro-4-nitrobenzoic acid (100 g, 540 mmol), EDCI (155.3 g, 810 mmol), NMM (178 mL. 1.62 mol) and N-methoxymethylamine hydrochloride (79.0 g, 810 mmol). The reaction mixture was stirred at room temperature for 17 h under nitrogen protection. Upon completion of the reaction, the reaction mixture was diluted with 1N hydrochloric acid (1 L) and transferred to a separatory funnel to separate the organic phase. The organic phase was washed sequentially with 1N sodium hydroxide solution (2 x 500mL) and water (250mL). All aqueous layers were back-extracted with ethyl acetate (2 × 500 mL). The organic layers were combined, dried with anhydrous magnesium sulfate, filtered and concentrated under reduced pressure to give 102.3 g (448 mmol, 83% yield) of a yellow solid product. The product was confirmed by NMR hydrogen spectroscopy (DMSO-d6): δ 8.22-8.18 (t, J=8.0 Hz, 1H), 7.79-7.76 (d, J=11.5 Hz, 1H), 7.60-7.58 (d, J=8.3 Hz, 1H), 3.56 (s, 3H), 3.28 (s, 3H); the mass spectrometry analysis showed that [M+H]+= 229.1; liquid chromatography-mass spectrometry analysis showed a retention time of 2.27 min.