Hydroxylamine → 2,3-Difluoro-6-(trifluoromethyl)benzamide

Participants

Reaction Conditions

Reaction Steps

Into a 2 L four-neck flask were added 95.0 g (1.44 mol) of 50% hydroxylamine aqueous solution, 960 ml of pure water, 7.6 g (0.09 mol) of sodium hydrogencarbonate, 480 ml of methanol, 0.09 g of 8-hydroxyquinoline and 124.3 g (0.06 mol) of 2,3-difluoro-6- trifluoromethylbenzonitrile (I″) at room temperature. After gradually raising temperature, the resulting solution was heated with stirring at 60° C. for 9 hours. It was conformed with HPLC that (I″) (tR 16.0 min) disappeared, 2,3 difluoro-6-trifluoromethylbenzamidoxime (II′) was mainly produced (yield 80.3%, tR 3.6 min) and 2,3-difluoro-6-trifluoromethylbenzamide (III′) was produced as a byproduct (yield 4.5%, tR 4.8min). Then, at about 45° C., methanol-water (about 800 g) in the reaction solution was removed under reduced pressure. The residue was extracted with 1.2 L of methyl-t-butylether (MTBE). The organic layer was washed with 120 ml of water, and hydrochlorinated and extracted with 300 ml of 7% hydrochloric acid. Further the organic layer was twice hydrochlorinated and extracted with 150 ml of 7% hydrochloric acid. The aqueous layers from the extraction after hydrochlorination were combined, cooled down below 15° C., neutralized with 170 g of 28% sodium-hydroxide aqueous solution, and extracted again with 300 ml of MTBE. The aqueous layer was further extracted with 300 ml of MTBE. The organic layers were combined, washed with 120 ml of water, and concentrated under reduced pressure to give 114 g of target 2,3-difluoro-6-trifluoromethylbenzamidoxime (II′) (m.p. 114 to 115° C., yield 78% and purity 98.7%).

Provenance & Evidence