反应详情

A mixture of 9.5 g of methyl 2-(2,4-difluorophenylamino)-5-fluoro-6-hydroxynicotinate, 26.5 g of phosphorus pentachloride and 46.9 g of phosphorus oxychloride was subjected to reaction at 70°-80° C. for 4 hours. Subsequently, the reaction mixture was gradually added to 285 ml of water, and the crystals thus deposited were collected by filtration and then washed with 57 ml of water. The crystals thus obtained were purified by a column chromatography [Wako Silica Gel C-200, eluant: toluene] to obtain 3.5 g (yield 34.7%) of methyl 6-chloro-2-(2,4-difluorophenylamino)-5fluoronicotinate having a melting point of 137°-139° C.

1. customwas subjected to reaction at 70°-80° C. for 4 hours
2. filtrationthe crystals thus deposited were collected by filtration
3. washwashed with 57 ml of water
4. customThe crystals thus obtained
5. customwere purified by a column chromatography [Wako Silica Gel C-200, eluant: toluene]