Patent ID: 6013796
Filing Date: 2000-01-11
Classification: A61P,C07D

Abstract:
A process of preparing naltrexone from morphine comprising the steps of:(1) protecting the hydroxy groups in the 3- and 6-positions of morphine so as to form 3(O),6(O)-diprotected-morphine wherein the 3-position protecting group P is benzyl or substituted benzyl and the 6-postion protecting group is an acyl group, R"" C(O), wherein R"" is lower alkyl of 1-4 carbon atoms;(2) de-methylating the N-methyl on the 17 position of the 3(O),6(O)-diprotected-morphine and hydrolizing the 6-acyl group so as to form 3(O)-protected-normorphine;(3) reacting the 3(O)-protected-normorphine with cyclopropylmethyl halide and a base so as to form 17-cyclopropylmethyl-3(O)-protected-normorphine;(4) oxidizing 17-cyclopropylmethyl-3(O)-protected-normorphine so as to form 17-cyclopropylmethyl-3(O)-protected-normorphinone:(5) converting 17-cyclopropylmethyl-3(O)-protected-normorphinone to the 17-cyclopropylmethyl-14-hydroxy-3(O)-protected-normorphinone by either (5a) or (5b):(5a) converting 17-cyclopropylmethyl-3(O)-protected-normorphinone to 17-cyclopropylmethyl-14-hydroxy-3(O)-protected-normorphinone;(5b) first, converting the 17-cyclopropylmethyl-3(O)-protected-normorphinone to the 17-cyclopropylmethyl-3(O)-protected-normorphinone dienol acylate, then, converting the latter to the 17-cyclopropylmethyl-14-hydroxy-3(O)-protected-normorphinone;(6) hydrogenating the 17-cyclopropylmethyl-14-hydroxy-3(O)-protected-normorphinone so as to form naltrexone.