Methylamine → 1-(5-Fluoro-2-(methylamino)phenyl)ethanone

참여 물질

반응 단계

A mixture of 2',5'-difluoroacetophenone (20 g), methylamine (33% w/w solution in industrial methylated spirit, 31ml), industrial methylated spirit (30 ml) and copper powder (0.2 g) was heated at 80° in a sealed pressure vessel for 24 hours. The reaction mixture was allowed to cool to ambient temperature and the mixture washed out of the vessel with industrial methylated spirit (2×30 ml). A solution of sodium sulphide nonahydrate (1 g) in water (10 ml) was added to the combined reaction mixture and washings and the mixture heated to 50° for 15 minutes. The mixture was filtered through diatomaceous earth (sold under the trade name CELITE) and the filter bed washed with industrial methylated spirit (50 ml). The combined filtrate and washings were evaporated to give an oil which was stirred with hydrochloric acid (5M, 80 ml) overnight. The mixture was adjusted to pH 8-9 using aqueous sodium hydroxide (specific gravity 1.5) and then extracted with dichloromethane (3×100 ml). The combined extracts were dried over magnesium sulphate and the solvent removed by distillation. The residue was extracted with diethyl ether (100 ml), the extract treated with activated charcoal (5 g) and the solvent removed by distillation. The residue was purified by flash chromatography on a silica gel column eluted with dichloromethane:petroleum ether (1:1) to give the novel compound 5'-fluoro-2'-(methylamino)acetophenone, m.p. 43°-45°.

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