Citric Acid → HCID 78324915, compound

Temperature

80 °C

Pyrrolidine (0.03 ml, 0.36 mmol) was added to a suspension of the tert-butyl 6-(3-formyl-4-methoxy-2-methylphenyl)-3-methylpyridine-2-carboxylate produced in Example 10-2 (1.31 g) and 5,5-dimethylcyclohexane-1,3-dione (1.17 g, 8.33 mmol) in ethanol (26.2 ml) at room temperature, and the mixture thus obtained was then stirred at 80° C. for 3 hours. After air-cooling, the solvent was distilled away from the reaction solution under reduced pressure. The residue thus obtained was dissolved in chloroform (26.2 ml), and p-toluenesulfonic acid monohydrate (0.19 g, 1.09 mmol) was then added to the solution obtained above at room temperature. The mixture thus obtained was stirred at 70° C. for 2.5 hours. After air-cooling, water was added to the reaction solution, and the mixed solution was then extracted with dichloromethane twice. The organic layer thus obtained was dried over anhydrous sodium sulfate, and the solvent was then distilled away under reduced pressure. The residue thus obtained was dissolved in dichloromethane (51 ml), and trifluoroacetic acid (25.5 ml) was then added to the solution obtained above at room temperature. The mixture thus obtained was stirred at the same temperature as above for 4.5 hours. Thereafter, the solvent was distilled away from the reaction solution under reduced pressure. A small amount of saturated aqueous solution of sodium hydrogen carbonate was added to the residue thus obtained, and thereafter, a 10% aqueous solution of citric acid was added thereto. The solution thus mixed was extracted with dichloromethane. The organic layer thus obtained was dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the residue thus obtained was then dissolved in THF (51 ml). A 1 N aqueous solution of sodium hydroxide (7.96 ml) was added to the solution obtained above, and the mixture thus obtained was then stirred at room temperature. Thereafter, water was added to the reaction solution, and the mixed solution was then washed with diethyl ether. A 1 N aqueous solution of hydrochloric acid (7.96 ml) was added to the water layer thus obtained, and the mixed solution was then extracted with dichloromethane. The organic layer thus obtained was dried over anhydrous sodium sulfate. The solvent was distilled away under reduced pressure, and the solid thus obtained was then washed with a mixed solution of diethyl ether and hexane, followed by collection by filtration and drying, to obtain the title compound (0.966 g, yield: 50%).

1. customthe mixture thus obtained
2. temperatureAfter air-cooling
3. distillationthe solvent was distilled away from the reaction solution under reduced pressure
4. customThe residue thus obtained
5. customobtained above at room temperature
6. customThe mixture thus obtained
7. stirringwas stirred at 70° C. for 2.5 hours
8. temperatureAfter air-cooling
9. extractionthe mixed solution was then extracted with dichloromethane twice
10. customThe organic layer thus obtained
11. dry with materialwas dried over anhydrous sodium sulfate
12. distillationthe solvent was then distilled away under reduced pressure
13. customThe residue thus obtained
14. customobtained above at room temperature
15. customThe mixture thus obtained
16. stirringwas stirred at the same temperature as above for 4.5 hours
17. distillationThereafter, the solvent was distilled away from the reaction solution under reduced pressure
18. additionA small amount of saturated aqueous solution of sodium hydrogen carbonate was added to the residue
19. customthus obtained
20. additionThe solution thus mixed
21. extractionwas extracted with dichloromethane
22. customThe organic layer thus obtained
23. dry with materialwas dried over anhydrous sodium sulfate
24. distillationThe solvent was distilled away under reduced pressure
25. customthe residue thus obtained
26. customobtained above, and the mixture
27. customthus obtained
28. stirringwas then stirred at room temperature
29. washthe mixed solution was then washed with diethyl ether
30. additionA 1 N aqueous solution of hydrochloric acid (7.96 ml) was added to the water layer
31. customthus obtained
32. extractionthe mixed solution was then extracted with dichloromethane
33. customThe organic layer thus obtained
34. dry with materialwas dried over anhydrous sodium sulfate
35. distillationThe solvent was distilled away under reduced pressure
36. customthe solid thus obtained
37. washwas then washed with a mixed solution of diethyl ether and hexane
38. filtrationfollowed by collection by filtration
39. customdrying

ORD record

ord-b6efd1d3add248178bc14b6a676da9db

Source dataset

uspto-grants-2015_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08975263B2