反应详情

A mixture of 2',3'-difluoroacetophenone (30 g), methylamine (33% w/w solution in industrial methylated spirit, 46.5 ml), industrial methylated spirit (20 ml) and copper powder (1 g) was stirred in a sealed pressure vessel overnight at 100°. 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 (3.7 g) in water (39 ml) was added and the mixture heated at 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 washing were evaporated to give an oil which was stirred with hydrochloric acid (5M, 120 ml) for 90 minutes. The mixture was neutralised with aqueous sodium hydroxide (5M, 120 ml) and then extracted with dichloromethane (2×150 ml, then 100 ml). The combined extracts were washed with aqueous sodium chloride (6M, 50 ml), dried over magnesium sulphate and evaporated to dryness. The residue was purified by flash chromatography on a silica gel column eluted with dichloromethane:methanol (19:1) to give the novel compound 3'-fluoro-2'-(methylamino)acetophenone, m.p. 26°-28°.

1. washthe mixture washed out of the vessel with industrial methylated spirit (2×30 ml)
2. additionA solution of sodium sulphide nonahydrate (3.7 g) in water (39 ml) was added
3. temperaturethe mixture heated at 50° for 15 minutes
4. filtrationThe mixture was filtered through diatomaceous earth (
5. washwashed with industrial methylated spirit (50 ml)
6. washThe combined filtrate and washing
7. customwere evaporated
8. customto give an oil which
9. extractionextracted with dichloromethane (2×150 ml
10. washThe combined extracts were washed with aqueous sodium chloride (6M, 50 ml)
11. dry with materialdried over magnesium sulphate
12. customevaporated to dryness
13. customThe residue was purified by flash chromatography on a silica gel column
14. washeluted with dichloromethane:methanol (19:1)