反应详情

温度

60 °C

At 55-65° C., a solution of 4-chloro-2-chloromethyl-3-methoxypyridinium chloride (10.0 kg, 43.8 mol) in water (20 L) was added over 2-3 h to a mixture of 5-difluoromethoxy-1H-benzimidazole-2-thiol (8.84 kg, 40.9 mol), toluene (43 L), water (21 L) and 40% aqueous NaOH (10.3 kg, 103 mol). Stirring at 60° C. was continued for 2-3 h before the reaction mixture was cooled to 10-15° C. The precipitate was centrifuged off, washed with toluene (16 L) and re-pulped in water (122 L). Centrifugation followed by an aqueous rinse (32 L) and drying at 35° C. in vacuo gave 5-difluoromethoxy-2-[(4-chloro-3-methoxy-2-pyridinyl)methylthio]-1H-benzimidazole mono hydrate (KF=4.6%) as an off-white solid (m. p. 95-99° C.); yield 14.2 kg (92%).

1. temperaturewas cooled to 10-15° C
2. washwashed with toluene (16 L) and re-pulped in water (122 L)
3. washan aqueous rinse (32 L)
4. customdrying at 35° C. in vacuo