反应详情

温度

50 °C

Dimethylpyridine-3,5-dicarboxylate (50 g) was dissolved in acetic acid (300 ml), 5% rhodium carbon (5 g) was added, and the mixture was stirred under pressurized hydrogen atmosphere (5 atm) at 50° C. for 15 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 ethanol (300 ml) and, under ice-cooling, triethylamine (107 ml) and di-tert-butyl dicarbonate (67 g) were successively added. 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 6 M hydrochloric acid. The mixture was extracted with ethyl acetate. The ethyl acetate extract 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 (250 ml), and 8 N aqueous sodium hydroxide solution (128 ml) was added dropwise at room temperature. The reaction mixture was stirred at room temperature for 24 hr, and methanol was evaporated under reduced pressure. The concentrated solution 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 6 M hydrochloric acid. The precipitated powder was collected by filtration, washed with water, and air-dried. The obtained powder (55 g) was dissolved in methanol (200 ml) by heating and the mixture was concentrated under reduced pressure until the amount of methanol became half. Water (50 ml) was added, and the mixture was stood at room temperature overnight. The precipitated white powder was collected by filtration, washed with cold methanol/water=2/1 (200 ml) and air-dried to give the object compound (38 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 ethanol (300 ml) and, under ice-
5. temperaturecooling
6. additiontriethylamine (107 ml) and di-tert-butyl dicarbonate (67 g) were successively added
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. extractionThe mixture was extracted with ethyl acetate
11. extractionThe ethyl acetate extract 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 (250 ml)
16. addition8 N aqueous sodium hydroxide solution (128 ml) was added dropwise at room temperature
17. stirringThe reaction mixture was stirred at room temperature for 24 hr
18. custommethanol was evaporated under reduced pressure
19. additionThe concentrated solution 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
24. dissolutionThe obtained powder (55 g) was dissolved in methanol (200 ml)
25. temperatureby heating
26. concentrationthe mixture was concentrated under reduced pressure until the amount of methanol
27. additionWater (50 ml) was added
28. waitthe mixture was stood at room temperature overnight
29. filtrationThe precipitated white powder was collected by filtration
30. washwashed with cold methanol/water=2/1 (200 ml)
31. customair-dried