反应详情

To a stirred and cooled (5°-10° C.) mixture of 15.2 parts of 4-amino-2-chloro-α-(4-chlorophenyl)-α,5-dimethylbenzeneacetonitrile, 14.4 parts of concentrate hydrochloric acid and 125 parts of acetic acid was added dropwise, during a 30 minutes period, a solution of 3.5 parts of sodium nitrite in 15 parts of water at about 10° C. Upon completion, the whole was stirred for 30 minutes and then 10 parts of sodium acetate and 7.8 parts of ethyl (2-cyanoacetyl)carbamate were added, during a period of 2 hours, at room temperature. The reaction mixture was poured into 500 parts of water. The product was filtered off, washed with water and dissolved in dichloromethane. The organic layer was dried, filtered and evaporated. The residue was purified by column chromatography over silica gel using a mixture of trichloromethane and methanol (95:5 by volume) as eluent. The pure fractions were collected and the eluent was evaporated in vacuo. The residue was stirred in 2-propanol. The product was filtered off, washed with 2,2'-oxybispropane and dried, yielding 17.5 parts (74.1%) of ethyl[2-[[5-chloro-4-[1-(4-chlorophenyl)-1-cyanoethyl]-2-methylphenyl]hydrazono]-2-cyanoacetyl]carbamate (intermediate 44).

1. temperaturecooled
2. additionwas added dropwise, during a 30 minutes period
3. customat about 10° C
4. stirringUpon completion, the whole was stirred for 30 minutes
5. filtrationThe product was filtered off
6. washwashed with water
7. dissolutiondissolved in dichloromethane
8. customThe organic layer was dried
9. filtrationfiltered
10. customevaporated
11. customThe residue was purified by column chromatography over silica gel using
12. additiona mixture of trichloromethane and methanol (95:5 by volume) as eluent
13. customThe pure fractions were collected
14. customthe eluent was evaporated in vacuo
15. stirringThe residue was stirred in 2-propanol
16. filtrationThe product was filtered off
17. washwashed with 2,2'-oxybispropane
18. customdried