Methylamine → 3-{4-[(3-Fluorophenyl)methoxy]phenyl}-N-methylbut-2-enamide

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Reaction Conditions

Reaction Steps

0.224 g (4 mmol) of KOH is dissolved in 10 ml methanol. 0.4 g (1.33 mmol) of 3-[4-(3-fluoro-benzyloxy)-phenyl]-but-2-enoic acid methyl ester is added and the resulting solution refluxed for 6 hours, concentrated and acidified with 2N aqueous hydrochloric acid. Extraction with ethyl acetate gives 325 mg (85%) of the crude acid. This acid is dissolved in 10 ml of dichloromethane, 2 drops of N,N-dimethylformamide are added and the mixture is cooled to 0° C. Slow addition of 0.380 g (3 mmol) of oxalylchloride yields a yellow solution which is stirred for additional 1.5 hours at RT. Evaporation of the reaction mixture leaves a yellowish resin which is dissolved in 5 ml THF and slowly added at 0° C. to a mixture of 5 ml THF and 5 ml aqueous methylamine (40%). The resulting slurry is stirred at RT for 1 hour, evaporated, diluted with water and extracted three times with ethyl acetate. Chromatography on silica gel (cyclohexane/ethyl acetate 1:1) gives 220 mg (50%) of a colorless solid. MS: m/e=300.2 (M++H).

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