Patent ID: 8664433

Claim:
A method for producing a crude preparation of 4-[3-(2,6-Dimethylbenzyloxy)phenyl]-4-oxobutanoic acid ethyl ester, comprising: (a) to a first solution in a reaction vessel, adding dropwise a second solution while maintaining the solution in the reaction vessel under an inert gas at a temperature below −50° C. under stirring conditions, wherein the first solution consists essentially of one equivalent of 1-[3-(2,6-Dimethylbenzyloxy)-phenyl]-ethanone dissolved in tetrahydrofuran and 1,3-Dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone, the first solution being cooled to a temperature between −35° C. and −75° C. and having a total water content of from 0.1 to 0.6 equivalents; and the second solution consists essentially of from 1.1 to 1.3 equivalents of lithium bis(trimethylsilyl)amide dissolved in tetrahydrofuran; (b) stirring the solution resulting from step (a) at a temperature between −35° C. and −75° C. for about 30 minutes; (c) to the solution from step (b), adding dropwise from 1 to 2 equivalents of ethyl bromoacetate while maintaining the temperature of the solution in the reaction vessel between −35° C. and −75° C.; (d) allowing the temperature of the solution from step (c) to warm to a temperature in a range from −40° C. to 0° C. and maintaining the solution at a temperature in said range for a sufficient time for completion of alkylation; (e) adding water or an aqueous salt solution to the solution from step (d) to quench; (f) to the organic solution from step (e), adding an organic solvent; (g) to the solution from step (f), separating the aqueous layer from the organic layer and discarding the aqueous layer; (h) washing the organic layer from the preceding step with a saturated aqueous sodium chloride solution; (i) concentrating the organic layer from step (h) to an oil, thereby yielding crude 4-[3-(2,6-Dimethylbenzyloxy)phenyl]-4-oxobutanoic acid ethyl ester.