N-methylation of the C3′ amide of taxanes:: Synthesis of N-methyltaxol C and N-methylpaclitaxel

A method has been developed for the methylation of the C3' amide of taxol C and paclitaxel. Taxol C and paclitaxel were sequentially silylated at the 2', 7, and 1-hydroxyl groups with tert-butyldimethylsilyl chloride, triethylsilyl chloride, and dimethylsilyl chloride, respectively. Subsequent reaction with potassium tert-butoxide and methyl iodide provided the corresponding N-methylated taxane derivatives. Removal of the silyl protecting groups furnished N-methyltaxol C and N-methylpaclitaxel.