反应详情

To a solution of 462 mg of Intermediate 39 in 20 ml of anhydrous acetonitrile, a solution of 320.2 mg of Intermediate 14 in 10 ml of anhydrous acetonitrile was added under argon atmosphere at 0° C. whereupon the reaction mixture was removed from the ice bath and was agitated for 115 minutes. To this mixture was then added a solution of 215 mg of sodium borohydride in 20 ml of absolute ethanol at room temperature. After agitation for 75 minutes, the reaction was terminated using 1 N hydrochloric acid (pH 4) and thereto was added 0.54 g of ethanolamine. After agitation for 10 minutes, the mixture was diluted with ethyl acetate,organic layer was rinsed with saturated aqueous sodium chloride solution and dried, whereupon it was evaporated under a reduced pressure. This was purified by a column chromatography (elution by methanol/ethyl acetate of 1/7), whereby 251.3 mg of fractions containing the free amine product of the above-identified compound were obtained. This was further purified by a PTLC (elution with methanol/ethyl acetate of 1/7), whereby 134.7 mg of free amine product of the above-identified compound were obtained. Rf=0.50 (methanol/ethyl acetate of 1/7). To this, 1.1 equivalent amount of 0.1 N hydrogen chloride/ethanol were added to convert it into hydrochloride salt (the above-identified compound), which was washed with ethanol, ethyl acetate and diethyl ether, successively, with subsequent drying under a reduced pressure, whereby 93.9 mg of the above-identified compound were obtained.

1. customwas removed from the ice bath
2. additionTo this mixture was then added a solution of 215 mg of sodium borohydride in 20 ml of absolute ethanol at room temperature
3. waitAfter agitation for 75 minutes
4. customthe reaction was terminated
5. additionwas added 0.54 g of ethanolamine
6. waitAfter agitation for 10 minutes
7. additionthe mixture was diluted with ethyl acetate,organic layer
8. washwas rinsed with saturated aqueous sodium chloride solution
9. customdried, whereupon it
10. customwas evaporated under a reduced pressure
11. customThis was purified by a column chromatography (elution by methanol/ethyl acetate of 1/7), whereby 251.3 mg of fractions
12. additioncontaining the free amine product of the above-identified compound
13. customwere obtained
14. customThis was further purified by a PTLC (elution with methanol/ethyl acetate of 1/7), whereby 134.7 mg of free amine product of the above-identified compound
15. customwere obtained
16. washwas washed with ethanol, ethyl acetate and diethyl ether
17. customsuccessively, with subsequent drying under a reduced pressure