反应详情

19.1 ml of a 4N sodium hydroxide solution and 3.5 g of methyl hydrazine are introduced into 76 ml of ethanol. At an internal temperature of <5° C., 4.5 ml of carbon disulfide are added dropwise with stirring, and the mixture is then stirred for 30 minutes. 17.0 g of 2-chloro-1-(5-chloro-3-fluoropyridin-2-yl)-propan-1-one (Example P36) are subsequently added in the course of 15 minutes at an internal temperature of <5° C. The temperature is then allowed to rise to 22° C. and the mixture is subsequently stirred for 30 minutes. TLC analysis (silica gel 60 F254; eluant: n-hexane/ethyl acetate, UV) of a worked-up sample shows that starting material is no longer present. 2.5 ml of a concentrated hydrochloric acid solution are then added dropwise to form a yellow precipitate. Stirring is carried out for 1 hour and the mixture is then poured into water and extracted with tert-butyl methyl ether. The combined ethereal phases are washed with water, dried over magnesium sulfate, filtered and concentrated to dryness in vacuo. 20.3 g of the desired title compound are obtained in the form of a solid having a melting point of 107-112° C.

1. stirringthe mixture is then stirred for 30 minutes
2. customare subsequently added in the course of 15 minutes at an internal temperature of <5° C
3. customto rise to 22° C.
4. stirringthe mixture is subsequently stirred for 30 minutes
5. customto form a yellow precipitate
6. stirringStirring
7. extractionextracted with tert-butyl methyl ether
8. washThe combined ethereal phases are washed with water
9. dry with materialdried over magnesium sulfate
10. filtrationfiltered
11. concentrationconcentrated to dryness in vacuo