To a solution of 4-(difluoromethoxy)benzonitrile (5 g, 30 mmol) in ethanol at 4° C. was bubbled dry HCl(g) for 3 h. The resulting mixture was stoppered and kept at 4° C. for 65 h. Ether (40 ml) was then added with ultrasonication to precipitate the imidate hydrochloride salt, which was washed twice with dry ether (40 ml) and then dried under vacuum (0.05 mmHg) at 20° C. To a solution of imidate hydrochloride salt (1 g, 4 mmol) in ethanol (15 ml) was added sodium ethoxide solution dropwise (sodium: 98 mg, 4 mmol in 5 ml of dry ethanol) at room temperature. The reaction was allowed to stir for a further 30 min then 3-[1,3]Dioxolan-2-yl-benzoic acid hydrazide was added (824 mg, 4 mmol) and the mixture was heated to reflux for 22 h until the starting materials were consumed. The reaction mixture was evaporated to dryness and chromatographed over SiO2 (Merck 230-400 mesh) eluting with EtOAc/nHexane (3:7), the product fractions were combined and evaporated to afford the title compound as a white solid (885 mg, 62% yield), MS: m/e=359.1 (M+).
