Patent ID: 6184395
Filing Date: 2001-02-06
Classification: A61P,C07D

Abstract:
A process for the preparation of paclitaxel or a paclitaxel analogue from a taxane precursor of formula I ##STR8##wherein:R.sub.1 =CH.sub.3, c-C.sub.6 H.sub.11, C.sub.6 H.sub.5, p-CH.sub.3 --C.sub.6 H.sub.4 or p-NO.sub.2 --C.sub.6 H.sub.4 ;R.sub.2 =CH.sub.3, CH.sub.2 CH.sub.3, CH.sub.2 CH.sub.2 CH.sub.3, C(CH.sub.3).sub.3, (CH.sub.2).sub.3 CH.sub.3,(CH.sub.2).sub.4 CH.sub.3, C.sub.6 H.sub.5, p-NO.sub.2 --C.sub.6 H.sub.4, c-C.sub.3 H.sub.5, c-C.sub.4 H.sub.7, c-C.sub.5 H9 or OCH.sub.3 ;R.sub.3 =(CH(CH.sub.3).sub.2).sub.2 OCH.sub.3, (CH.sub.2 CH.sub.3).sub.3, (CH.sub.3).sub.3 or (C(CH.sub.3).sub.3)(CH.sub.3).sub.2 ;R.sub.4 =H, CH.sub.3, C.sub.6 H.sub.5, COCH.sub.3, COC.sub.6 H.sub.5 or COC.sub.4 H.sub.9 ;R.sub.5 = ##STR9##R.sub.6 =H, F, OH, OCH.sub.3, OSi(CH.sub.2 CH.sub.3).sub.3, OSi(C(CH.sub.3).sub.3)(CH.sub.3).sub.2 or OC(CH.sub.3).sub.2 OCH.sub.3, provided that R.sub.6 is other than OC(CH.sub.3).sub.2 OCH.sub.3 when R.sub.1 is C.sub.6 H.sub.5, R.sub.2 is CH.sub.3, R.sub.3 is (CH.sub.2 CH.sub.3).sub.3, R.sub.4 is COCH.sub.3, R.sub.7 is C.sub.6 H.sub.5 and R.sub.8 is C.sub.6 H.sub.5 ;R.sub.7 =C.sub.6 H.sub.5, C(CH.sub.3).sub.3 or CH(CH.sub.3).sub.2 ;R.sub.8 =C.sub.6 H.sub.5, C(CH.sub.3).sub.3, (CH.sub.3).sub.3 CO, (CH.sub.3).sub.3 CCH.sub.2, CH.sub.3 (CH.sub.2).sub.3 O, 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.