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

Participants

Reaction Steps

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%).

Provenance & Evidence