Reaction conditions for the cleavage of silyl ethers in the preparation of paclitaxel(taxol®) and paclitaxel analogues

A process for the preparation of paclitaxel or a paclitaxel analogue from a taxane precursor of formula I

• wherein:
• R1=CH3, c-C6H11, C6H5, p-CH3—C6H4 or p-NO2—C6H4;
• R2=CH3, CH2CH3, CH2CH2CH3, C(CH3)3, (CH2)3CH3,(CH2)4CH3, C6H5, p-NO2—C6H4, c-C3H5, c-C4H7, c-C5H9 or OCH3;
• R3=(CH(CH3)2)2OCH3, (CH2CH3)3, (CH3)3 or (C(CH3)3)(CH3)2;
• R4=H, CH3, C6H5, COCH3, COC6H5 or COC4H9;
• R5=
• R6=H, F, OH, OCH3, OSi(CH2CH3)3, OSi(C(CH3)3)(CH3)2 or OC(CH3)2OCH3, provided that R6 is other than OC(CH3)2OCH3 when R1 is C6H5, R2 is CH3, R3 is (CH2CH3)3, R4 is COCH3, R7 is C6H5 and R8 is C6H5;
• R7=C6H5, C(CH3)3 or CH(CH3)2;
• R8=C6H5, C(CH3)3, (CH3)3CO, (CH3)3CCH2, CH3(CH2)3O, cyclobutyl, cyclohexyloxy or 2-furyl;
• which process comprises the steps of:
• (a) preparing a solution of taxane precursor in a weak organic acid;
• (b) preparing a solution comprised of a strong acid in said weak organic acid and water;
• (c) adding the solution from step (b) to step (a);
• (d) stirring the reaction mixture formed in step (c);
• (e) quenching said reaction mixture;
• (f) adding water and extracting the product using an organic solvent;
• (g) separating the organic layer from the aqueous layer;
• and
• (h) isolating the product from said organic layer.