Hydrochloric Acid → Caspofungin Acetate

Participants

Reaction Steps

Under N2, the compound of Formula 4 (1.0 g), phenyl boronic acid (0.36 g), tetrahydrofuran (40 ml) were refluxed for 30 min. The reaction mixture was cooled to the room temperature, and BSTFA (2.0 ml) was added and the solution was agitated for 1 h at the room temperature. The temperature was maintained at −20 to −15° C., and the complex of borane and tetrahydrofuran in tetrahydrofuran (6.8 ml, 1 M) was added dropwise. Upon addition, the reaction was conducted at −20 to −15° C. for 3.5 h. The conversion rate for the reaction was 81% 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 (0.77 g, yield 77%, the purity=98.3% 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 (11 ml) was added dropwise. The whole system was agitated for 1 h at 10° C., and filtered, and the obtained solid was dried to obtain caspofungin diacetate (the compound of Formula 1) (0.72 g, yield 72%).

Provenance & Evidence