Dimethylformamide → 2-Bromo-3-fluoro-6-nitrobenzamide

Participants

Reaction Conditions

Reaction Steps

2-Bromo-3-fluoro-6-nitrobenzoic acid (Example 134f) (24.83 g, 94.0) mmol, (mixture of two regioisomers) was dissolved in anhydrous THF (200 mL) under a nitrogen atmosphere at room temperature. Anhydrous DMF (0.75 mL) was added and the obtained mixture was cooled to 0° C. Oxalyl chloride (12.3 mL, 141 mmol) was slowly added and the reaction mixture was stirred at 0° C. for 10 min, and at room temperature for a further 2 h. The reaction was evaporated to dryness, suspended in anhydrous THF (100 mL) and added slowly to concentrated ammonium hydroxide (350 mL) at 0° C. After stirring for 45 minutes at 0° C. the mixture was extracted with CH2Cl2 (5×100 mL), and the organic extractions were then discarded. At this point the desired regioisomer existed as an insoluble precipitate in the aqueous layer, which was collected by filtration to give 10.3 g (42%) of 2-bromo-3-fluoro-6-nitrobenzamide which was used without further purification. 1H NMR (400 MHz, DMSO-d6) δ 8.27 (dd, J=8.8, 4.4 Hz, 1H), 8.10 (broad s, 1H), 7.95 (broad s, 1H), 7.66 (dd, J=9.6, 7.6 Hz, 1H).

Provenance & Evidence