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

Temperature

0 °C

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).

1. waitat room temperature for a further 2 h
2. customThe reaction was evaporated to dryness
3. additionadded slowly to concentrated ammonium hydroxide (350 mL) at 0° C
4. stirringAfter stirring for 45 minutes at 0° C. the mixture
5. extractionwas extracted with CH2Cl2 (5×100 mL)
6. extractionthe organic extractions
7. filtrationwas collected by filtration

ORD record

ord-b24b9a64e9d64defb7ee8337641f166e

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181276B2