反应详情

Thionyl chloride (100 mL) was added to 4-chloronicotinic acid (22.4 g), and the mixture was stirred with heating under reflux for 4 hr, and concentrated under reduced pressure. To a solution (300 mL) of the residue in methylene chloride were added N,O-dimethylhydroxylamine hydrochloride (13.8 g) and triethylamine (60 mL), and the mixture was stirred at room temperature for 5 hr. Water was added to the reaction mixture, and the reaction mixture was extracted with methylene chloride. The extract was dried over sodium sulfate, and concentrated under reduced pressure. To a solution (300 mL) of the residue in tetrahydrofuran was added a 3.0 M solution (54 mL) of methylmagnesium chloride in ether at −78° C. and the mixture was stirred under nitrogen atmosphere at room temperature for 10 hr. The reaction mixture was acidified with aqueous sodium carbonate solution to pH=9, and extracted with ethyl acetate. The extract was dried over sodium sulfate, and concentrated under reduced pressure to give a colorless oil. To a mixture of the obtained oil, ethyl mercaptoacetate (21 mL) and anhydrous N,N-dimethylformamide (200 mL) was added sodium hydride (60%, oily, 7.34 g) at 5° C. over 30 min, and the mixture was stirred at 5° C. for 20 min then at room temperature for 18 hr. Water was added to quench the reaction, and the reaction mixture was extracted with ethyl acetate. The extract was dried over sodium sulfate, and concentrated under reduced pressure. The obtained solid was recrystallized from petroleum ether/ethyl acetate to give the title object compound (5.45 g, 17%) as a white solid.

1. temperaturewith heating
2. temperatureunder reflux for 4 hr
3. concentrationconcentrated under reduced pressure
4. additionTo a solution (300 mL) of the residue in methylene chloride were added N,O-dimethylhydroxylamine hydrochloride (13.8 g) and triethylamine (60 mL)
5. stirringthe mixture was stirred at room temperature for 5 hr
6. additionWater was added to the reaction mixture
7. extractionthe reaction mixture was extracted with methylene chloride
8. dry with materialThe extract was dried over sodium sulfate
9. concentrationconcentrated under reduced pressure
10. additionTo a solution (300 mL) of the residue in tetrahydrofuran was added a 3.0 M solution (54 mL) of methylmagnesium chloride in ether at −78° C.
11. stirringthe mixture was stirred under nitrogen atmosphere at room temperature for 10 hr
12. extractionextracted with ethyl acetate
13. dry with materialThe extract was dried over sodium sulfate
14. concentrationconcentrated under reduced pressure
15. customto give a colorless oil
16. stirringthe mixture was stirred at 5° C. for 20 min
17. customto quench
18. customthe reaction
19. extractionthe reaction mixture was extracted with ethyl acetate
20. dry with materialThe extract was dried over sodium sulfate
21. concentrationconcentrated under reduced pressure
22. customThe obtained solid was recrystallized from petroleum ether/ethyl acetate