One pot synthesis of taxane derivatives and their conversion to paclitaxel and docetaxel

Protection of C-7, 10 Hydroxy Groups and Attachment of a Beta-Lactam Side Chain in a One Pot Reaction

[0116] As shown in FIG. 1, to a stirred solution of 10-deacetylbaccatin III (10-DAB), in an organic solvent, such as THF, at around room temperature under an argon atmosphere was treated with a hydroxy-protecting agent, such as Boc2O, in the presence of a base, such as 4-(N,N-dimethylamino)pyridine or n-BuLi or a mixture of n-BuLi / Li-t-OBu. The reaction was stirred at this temperature for a period between 30 minutes to 2 hours until complete consumption of the starting materials, as evidenced by TLC.

[0117] To this first solution of the C-7,10 protected 10-deacetylbaccatin III derivative in an organic solvent, such as the freshly distilled THF, under argon atmosphere at low temperature most preferably at −40 to −50° C., was added drop wise a solution of a base, such as n-BuLi, in hexanes or a mixture of n-BuLi / Li-t-OBu. After stirring for 30 min to 1 hr at this temperature, a soluti...

Synthesis of Docetaxel

[0118] As further shown in FIG. 1, the C-13 beta-lactam protected taxane intermediate, was hydrolyzed using formic acid to remove the C-7 and / or C-10 BOC protecting group and then with a mixture of NaHCO3 / Na2CO3 / H2O2 to deprotect the C-2′ and / or C-10 acetate groups to yield docetaxel, as described in U.S. patent application Ser. No. 10 / 790,622, which application is assigned to the assignee of the present invention and is incorporated herein by reference in its entirety.