反应详情

Under N2, the compound of Formula 4 (1.0 g), phenyl boronic acid (0.14 g), tetrahydrofuran (40 ml) were refluxed for 30 min. The reaction mixture was cooled to the room temperature, and BSTFA (1.06 ml) was added and the solution was agitated for 1 h at the room temperature. The reaction mixture was cooled to −10 to −5° C., and the complex of borane and dimethyl sulfide (0.4 ml, 0.94%) was added dropwise. Upon addition, the reaction mixture was warmed to 10 to 15° C., and the reaction was conducted for 3.5 h. The conversion rate for the reaction was 82% monitored by HPLC. Afterwards, 2 N hydrochloric acid (2.4 ml) was added dropwise, and water (80 ml) was added. Upon addition, the reaction mixture was agitated for 24 h at the room temperature. The reaction was diluted with water, and loaded onto a preparative column. The column was eluted with 22% acetonitrile/water (0.15% acetic acid). The collections rich in the product were pooled, diluted with water for one time and loaded onto a preparative column. The column was eluted with 90% acetonitrile/water (0.15% acetic acid), and effluents were collected and lyophilized to obtain the crude caspofungin diacetate (0.80 g, yield 80%, the purity=98.0% by HPLC) in white solid. The crude caspofungin was dissolved into ethanol (6 ml) and 6% aqueous acetic acid (0.6 ml), and then ethyl acetate (10.5 ml) was added dropwise. The whole system was agitated for 1 h at 10° C. and then filtered, and the obtained solid was dried to obtain caspofungin diacetate (the compound of Formula 1) (0.75 g, yield 75%).

1. additionwas added
2. temperatureThe reaction mixture was cooled to −10 to −5° C.
3. additionUpon addition
4. temperaturethe reaction mixture was warmed to 10 to 15° C.
5. waitthe reaction was conducted for 3.5 h
6. additionUpon addition
7. stirringthe reaction mixture was agitated for 24 h at the room temperature
8. washThe column was eluted with 22% acetonitrile/water (0.15% acetic acid)
9. additiondiluted with water for one time
10. washThe column was eluted with 90% acetonitrile/water (0.15% acetic acid), and effluents
11. customwere collected
12. customto obtain the crude caspofungin diacetate (0.80 g, yield 80%
13. stirringThe whole system was agitated for 1 h at 10° C.
14. filtrationfiltered
15. customthe obtained solid was dried