反应详情

To a solution of crude (2-methyl-3-amino-4-chlorophenoxy)acetonitrile (11.53 g) in toluene (PhMe) (60 mL) was added methanesulfonyl chloride (MsCl) (4.5 mL, 6.7 g) and the resultant solution was warmed to 35-40° C. Pyridine (py) (4.7 mL, 4.6 g) was then added slowly over 2 h. The resultant mixture was permitted to cool to ambient temperature and stirred for 24 h. The crude product mixture was then partitioned between 1N hydrochloric acid (100 mL), and a mixture of ethyl acetate (300 mL) and tetrahydrofuran (100 mL). The organic phase was washed with water, then concentrated to ca. 200 mL, leading to crystallization of the desired product. The white crystalline product was collected, rinsed with toluene, and dried to afford 10.40 g (65.1% field) of N-(6-chloro-3-cyanomethoxy-2-methylphenyl)-methanesulfonamide (>97% pure by HPLC). This material could optionally be recrystallized from isopropanol.

1. customThe crude product mixture was then partitioned between 1N hydrochloric acid (100 mL)
2. additiona mixture of ethyl acetate (300 mL) and tetrahydrofuran (100 mL)
3. washThe organic phase was washed with water
4. concentrationconcentrated to ca. 200 mL
5. customleading to crystallization of the desired product
6. customThe white crystalline product was collected
7. washrinsed with toluene
8. customdried