2-Propanone, 1-(2-fluoro-3-methoxy-6-nitrophenyl)-

Synthesis

1,2-Difluoro-3-(2,2-dimethoxypropyl)-4-nitrobenzene (16.2 g, 62 mmol) was used as a raw material and dissolved in methanol (200 ml) at 5 °C. To this solution was added freshly prepared sodium methanol solution (prepared by the reaction of sodium (1.71 g) and methanol (35 ml)). The reaction mixture was gradually warmed up to room temperature and stirred continuously for 3 days. After completion of the reaction, the volatiles were removed by distillation under reduced pressure. The residue was extracted by partitioning with ethyl acetate and 2N hydrochloric acid (1 ml). After the organic layer was concentrated to about 100 ml, THF (100 ml) and 6N hydrochloric acid (25 ml) were added and stirred at room temperature for 1 hour. The volatiles were again removed by distillation under reduced pressure and the residue was extracted by partition with ethyl acetate and water. The organic layer was separated and washed sequentially with water and brine, then dried with anhydrous magnesium sulfate and finally the solvent was evaporated. The residue was purified by column chromatography (eluent: ethyl acetate/petroleum ether, 3/7) to afford the target product 3-acetylmethyl-2-fluoro-1-methoxy-4-nitrobenzene (12.7 g, 90% yield).MS-ESI: 250 [MNa]+. 1H NMR (CDCl3): δ 2.38 (s, 3H), 4.0 (s, 3H), 4.25 ( s, 2H), 7.0 (dd, 1H), 8.05 (d, 1H).

References

[1] Patent: US2003/199491, 2003, A1
[2] Patent: US2003/212055, 2003, A1
[3] Patent: US2003/207878, 2003, A1