Ethyl orthoformate → 2-Fluoro-4-(methylamino)benzonitrile

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Reaction Steps

To a solution of 2-fluoro-4-aminobenzonitrile [Ind. Chim. Belg., 39, 490-500 (1974)] (3.8 g, 28 mmol) in anhydrous triethyl orthoformate (50 mL) was added trifluoroacetic acid (0.16 g, 1.4 mmol). The solution was heated to reflux 45 min, cooled and concentrated to give a yellow crystalline solid. To a solution of this solid in absolute ethanol (60 mL) at 0° C. was added sodium borohydride (3.2 g, 84 mmol). The resulting suspension was stirred at RT for 20 min, heated at reflux for 1 h, cooled and concentrated to give a colorless solid. This residue was partitioned between ether and water and the aqueous layer was extracted with ether. The organic phases were combined, washed with brine and dried (sodium sulfate). Concentration gave a white solid which was slurried in 35% ethyl acetate:hexane (200 mL) and filtered to give the title compound (3.7 g, 88%). mp 110-112° C.; 1H NMR (400 MHz, CDCl3) δ 7.35 (m, 1H), 6.4 (dd, 1H), 6.3 (dd, 1H), 2.9 (s, 3H).

Provenance & Evidence