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

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°.

1. temperaturewas heated at 80° in a sealed pressure vessel for 24 hours
2. washthe mixture washed out of the vessel with industrial methylated spirit (2×30 ml)
3. additionA solution of sodium sulphide nonahydrate (1 g) in water (10 ml) was added to the combined reaction mixture and washings
4. temperaturethe mixture heated to 50° for 15 minutes
5. filtrationThe mixture was filtered through diatomaceous earth (
6. washwashed with industrial methylated spirit (50 ml)
7. customThe combined filtrate and washings were evaporated
8. customto give an oil which
9. extractionextracted with dichloromethane (3×100 ml)
10. dry with materialThe combined extracts were dried over magnesium sulphate
11. customthe solvent removed by distillation
12. extractionThe residue was extracted with diethyl ether (100 ml)
13. additionthe extract treated with activated charcoal (5 g)
14. customthe solvent removed by distillation
15. customThe residue was purified by flash chromatography on a silica gel column
16. washeluted with dichloromethane:petroleum ether (1:1)

ORD record

ord-7e549fd6b84e4215b557aedba5db22ba

Source dataset

uspto-grants-1991_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04997840