Dimethylformamide → N-methoxy-3-(methoxymethyl)-N-methylbenzamide

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Reaction Steps

To a stirred solution of 3-(methoxymethyl)benzoic acid (20.9 g, 125.8 mmol) in dichloromethane (250 mL), cooled to 0° C. with a brine/ice bath, was added N,N-dimethylformamide (0.48 mL, 6 mmol) followed by oxalyl chloride (13.2 mL, 150.9 mmol). The resulting mixture was stirred 4 h at room temperature, until gas evolution stopped and a clear solution was obtained. The mixture was cooled to 0° C. with a brine/ice bath, N,O-Dimethylhydroxylamine (17.2 g, 176 mmol) was added at once, followed by dropwise addition of triethylamine (70.1 mL, 503 mmol) through a dropping funnel, while keeping the internal temperature below 10° C. The resulting suspension was stirred overnight at room temperature, diluted with water (400 mL). The aqueous layer was extracted with dichloromethane (2×250 mL) and the organic layer was washed with water (2×150 mL). The combined organic layers were dried (MgSO4) and concentrated in vacuo. Purification over silica gel afforded N-methoxy-3-(methoxymethyl)-N-methylbenzamide as a yellow oil [19.4 g, yield 63%; HPLC/MS:m/z=210 (M+H); log P(HCOOH)=1.43].

Provenance & Evidence