反应详情

温度

50 °C

Dimethyl pyridine-3,5-dicarboxylate (62.8 g) was dissolved in acetic acid (300 mL), 5% rhodium-carbon (6 g) was added and the mixture was stirred under hydrogen pressurization (5 atm) at 50° C. for 20 hr. The reaction mixture was allowed to cool to room temperature, the rhodium catalyst was filtered off, and the filtrate was concentrated under reduced pressure. The residue was dissolved in methanol (300 mL), and triethylamine (180 mL) and di-tert-butyl bicarbonate (105 g) were successively added under ice-cooling. The reaction mixture was stirred at room temperature for 15 hr, and concentrated under reduced pressure. The residue was dissolved in water, and the mixture was adjusted to pH 3 with 6M hydrochloric acid and extracted with ethyl acetate. The ethyl acetate extraction layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure. The residue was dissolved in methanol (300 mL), and 8N aqueous sodium hydroxide solution (161 mL) was added dropwise at room temperature. The reaction mixture was stirred at room temperature for 20 hr, and methanol was evaporated under reduced pressure. The concentrate was diluted with saturated aqueous sodium hydrogen carbonate solution (100 ml) and washed twice with diethyl ether. The basic aqueous layer was acidified (pH 3) with 6M hydrochloric acid. The precipitated powder was collected by filtration, washed with water and air-dried to give the object product (80.5 g) as a powder.

1. temperatureto cool to room temperature
2. filtrationthe rhodium catalyst was filtered off
3. concentrationthe filtrate was concentrated under reduced pressure
4. dissolutionThe residue was dissolved in methanol (300 mL)
5. additiontriethylamine (180 mL) and di-tert-butyl bicarbonate (105 g) were successively added under ice-
6. temperaturecooling
7. stirringThe reaction mixture was stirred at room temperature for 15 hr
8. concentrationconcentrated under reduced pressure
9. dissolutionThe residue was dissolved in water
10. extractionextracted with ethyl acetate
11. extractionThe ethyl acetate extraction layer
12. washwas washed with saturated brine
13. dry with materialdried over anhydrous sodium sulfate
14. customThe solvent was evaporated under reduced pressure
15. dissolutionThe residue was dissolved in methanol (300 mL)
16. addition8N aqueous sodium hydroxide solution (161 mL) was added dropwise at room temperature
17. stirringThe reaction mixture was stirred at room temperature for 20 hr
18. custommethanol was evaporated under reduced pressure
19. additionThe concentrate was diluted with saturated aqueous sodium hydrogen carbonate solution (100 ml)
20. washwashed twice with diethyl ether
21. filtrationThe precipitated powder was collected by filtration
22. washwashed with water
23. customair-dried