反应详情

The compound of formula 3a (100 g), 10% palladium carbon (10 g) and triethanolamine (2 g) were suspended in methanol and then hydrogenated at 40-45° C. for 2 h. After completion of the reaction (TLC monitoring), filtered the reaction mass to remove palladium carbon. cp. HCl (62 mL) was added to the filtrate, heated to reflux and maintained for 2 h. The reaction mass was cooled to ambient temperature, pH of the reaction mass was adjusted to 6.0-7.0 with 20% sodium hydroxide solution. Methanol was distilled off under vacuum at below 50° C. The resultant residue was dissolved in a mixture of isopropyl alcohol (300 mL) and purified water (600 mL) and pH was further adjusted to 9.0-10.0 with 20% sodium hydroxide solution at ambient temperature. The reaction mass was maintained for 10 h, cooled to 0-5° C., filtered and washed with purified water. The wet cake was suspended in isopropyl alcohol (350 mL), heated to reflux, and maintained for 30 min. The reaction mass was cooled to 2-4° C., maintained for 1 h., filtered and washed with isopropyl alcohol. The wet product was air dried to obtain the compound of formula 4 in 71.3 g (yield-95%) with HPLC purity of 99.76%.

1. customAfter completion of the reaction (TLC monitoring)
2. filtrationfiltered the reaction mass
3. customto remove palladium carbon
4. additionHCl (62 mL) was added to the filtrate
5. temperatureheated
6. temperatureto reflux
7. temperaturemaintained for 2 h
8. distillationMethanol was distilled off under vacuum at below 50° C
9. dissolutionThe resultant residue was dissolved in a mixture of isopropyl alcohol (300 mL)
10. custompurified water (600 mL)
11. custompH was further adjusted to 9.0-10.0 with 20% sodium hydroxide solution at ambient temperature
12. temperatureThe reaction mass was maintained for 10 h
13. temperaturecooled to 0-5° C.
14. filtrationfiltered
15. washwashed with purified water
16. temperatureheated
17. temperatureto reflux
18. temperaturemaintained for 30 min
19. temperatureThe reaction mass was cooled to 2-4° C.
20. temperaturemaintained for 1 h.
21. filtrationfiltered
22. washwashed with isopropyl alcohol
23. customdried