反应详情

549 mg (1.72 mmol) 5-Chloro-6-(1,4-dioxa-spiro[4.5]dec-8-yloxy)-isoquinoline (78) were dissolved in 20 ml THF/H2O (3:1). 1 ml TFA was added and the mixture was stirred at room temperature. After 1 h, 2 ml TFA were added and the temperature was increased to 50° C. After 5 d at 50° C., 2 ml TFA were added. After one additional day, 2 ml TFA were added and the temperature was increased to 100° C. After 5 h, the reaction was allowed to cool down to room temperature and the mixture was diluted with dichloromethane and H2O, Solid NaHCO3 was added for neutralization. The phases were separated and the aqueous phase was extracted with dichloromethane. The combined organic layers were dried over MgSO4 and evaporated. After final purification by preparative HPLC, 533 mg of the title compound as trifluoroacetate were obtained. Rt=0.88 min (Method #4). Detected mass: 276.2/278.2 (M+H+).

1. temperaturethe temperature was increased to 50° C
2. waitAfter 5 d at 50° C.
3. temperaturethe temperature was increased to 100° C
4. waitAfter 5 h
5. temperatureto cool down to room temperature
6. additionwas added for neutralization
7. customThe phases were separated
8. extractionthe aqueous phase was extracted with dichloromethane
9. dry with materialThe combined organic layers were dried over MgSO4
10. customevaporated
11. customAfter final purification by preparative HPLC, 533 mg of the title compound as trifluoroacetate
12. customwere obtained