Patent ID: RE39383

Claim:
An improved process for selective alkylation of a hydroxy group at the 6-position of a compound of the formula: wherein: R 1 and R 2 are independently hydrogen or a hydroxy-protecting group, except that R 1 and R 2 may not both be hydrogen simultaneously; Y is selected from the group consisting of a) oxygen, b) an oxime having the formula N-O-R 3 , wherein R 3 is selected from the group consisting of hydrogen, a loweralkenyl group, an aryl(loweralkyl) group, or a substituted aryl(loweralkyl) group; and c) to oxime having the formula: wherein R 4 is a loweralkyl group, a cycloalkyl group; a phenyl group, an aryl(loweralkyl) group; or R 4 and R 5 or R 4 and R 6 and the atoms to which they and attached are taken together form a 5- to 7-membered ring containing one oxygen atom; R 5 is a loweralkyl group; a loweralkoxymethyl group; or R 5 and R 4 and the atoms to which they are attached are taken together form a 5- to 7-membered ring containing one oxygen atom, or R 5 and R 6 and the atoms to which they are attached are taken together form a 5- to 7-membered cycloalkyl group; and R 6 is a hydrogen atom, a loweralkyl group, a phenyl group, an aryl(loweralkyl) group; or R 6 and R 4 and the atoms to which they are attached are taken together form a 5- to 7-membered ring containing one oxygen atom; or R 6 and R 5 and the atoms to which they are attached are taken together form a 5- to 7-membered cycloalkyl group; with the requirement that only one pair of substituents (R 4 and R 5 ), (R 4 and R 6 ) or (R 5 and R 6 ) may be taken together with the atoms to which they are attached to form a ring as defined above; and Z is hydrogen, hydroxy or protected-hydroxy; comprising reacting the compound with an alkylating agent in the presence of both a strong alkali metal base and a weak organic amine base in polar aprotic solvent or a mixture of polar aprotic solvents maintained at a reaction temperature for a period of time sufficient to complete the alkylation, by adding the weak organic base prior to the addition of the alkylating agent and the strong alkali metal base.