反应详情

6.50 g (46.7 mmol) of the compound from Example 72A were introduced into 20 ml of methanol at RT, 46.7 ml (46.7 mmol) of a 1N aqueous sodium hydroxide solution were added, and the mixture was stirred at RT for 2 h. Concentrated hydrochloric acid was then added until the pH was 2, the mixture was extracted with diethyl ether, and the combined organic phases were dried over sodium sulfate, filtered and concentrated. The residue was taken up in 8.5 ml (117 mmol) of thionyl chloride and stirred at 65° C. for 4 h. Cooling was followed by concentration, and the residue was twice taken up in diethyl ether and again concentrated each time. The residue was introduced into 17 ml of dichloromethane, 3.43 g (35.1 mmol) of N,O-dimethylhydroxylamine hydrochloride and 9.8 ml (70.3 mmol) of triethylamine were added, and the mixture was stirred at RT overnight. Water was added, the phases were separated, two extractions with dichloromethane were carried out, and the combined organic phases were dried over sodium sulfate, filtered and concentrated. The crude product was purified by flash chromatography on silica gel (mobile phase: dichloromethane/methanol 9/1) to result in 1.72 g (24% of theory) of the title compound.

1. extractionthe mixture was extracted with diethyl ether
2. dry with materialthe combined organic phases were dried over sodium sulfate
3. filtrationfiltered
4. concentrationconcentrated
5. stirringstirred at 65° C. for 4 h
6. temperatureCooling
7. concentrationwas followed by concentration
8. concentrationagain concentrated each time
9. additionwere added
10. stirringthe mixture was stirred at RT overnight
11. customthe phases were separated
12. extractiontwo extractions with dichloromethane
13. dry with materialthe combined organic phases were dried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated
16. customThe crude product was purified by flash chromatography on silica gel (mobile phase: dichloromethane/methanol 9/1)