Hydrazine hydrate (1:1) → HCID 67280404, compound

2-(Chloromethyl)-4-methoxy-3,5-dimethylpyridine (125.95 g) was added to a mixture of hydrazine monohydrate (360 ml) and methanol (3.3 L) under cooling in an ice bath, and the mixture was stirred for 30 minutes. Then, the ice bath was removed and the mixture was heated with stirring at 60° C. for 2.5 hours. After cooling to room temperature, water (1.5 L) was added to the reaction mixture, and about 3.5 L of the solvent was evaporated under reduced pressure. A 2 N sodium hydroxide solution (1 L) and sodium chloride (300 g) were added to the resulting concentrated residue, followed by extraction with dichloromethane. The organic layer was dried over anhydrous sodium sulfate and filtered. Then, the filtrate was concentrated under reduced pressure. The resulting residue was dissolved in dichloromethane (1.5 L). A 4 N solution of hydrochloric acid in dioxane (550 ml) was added under cooling in an ice bath, and then the mixture was stirred at −2° C. for 13 hours. The precipitated solid was collected by filtration, sequentially washed with dichloromethane, isopropyl ether and dichloromethane, and then dried to obtain the title compound (112.6 g, 68%).

1. temperatureunder cooling in an ice bath
2. customThen, the ice bath was removed
3. temperaturethe mixture was heated
4. stirringwith stirring at 60° C. for 2.5 hours
5. additionwater (1.5 L) was added to the reaction mixture, and about 3.5 L of the solvent
6. customwas evaporated under reduced pressure
7. additionA 2 N sodium hydroxide solution (1 L) and sodium chloride (300 g) were added to the resulting concentrated residue
8. extractionfollowed by extraction with dichloromethane
9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
10. filtrationfiltered
11. concentrationThen, the filtrate was concentrated under reduced pressure
12. dissolutionThe resulting residue was dissolved in dichloromethane (1.5 L)
13. additionA 4 N solution of hydrochloric acid in dioxane (550 ml) was added
14. temperatureunder cooling in an ice bath
15. stirringthe mixture was stirred at −2° C. for 13 hours
16. filtrationThe precipitated solid was collected by filtration
17. washsequentially washed with dichloromethane, isopropyl ether and dichloromethane
18. customdried

ORD record

ord-c4e991d21e0c4598a4b8976f0a1ba420

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08158638B2