Patent ID: 6864390

Claim:
A process for the preparation of a compound of Formula I: wherein R is C 1 -C 10 alkyl or C 3 -C 10 cycloalkyl, and pharmaceutically acceptable salts thereof, which comprises: a) adding a cyanoacetate of formula (A): wherein R 1 is alkyl or benzyl, to a mixture of a chiral cyclopentanone of formula (1): a solvent, a carboxylic acid, and a Knoevenagel reaction catalyst, and stirring the mixture in the presence of a means of removing water to produce the alkene of formula (2): b) adding the product of Step a) above to a mixture of benzylmagnesium chloride, benzylmagnesium bromide, or benzylmagnesium iodide, in a solvent to produce the addition products of formulas (3a): and (3b): c) adding the products of Step b) above to a mixture of a base selected from potassium hydroxide, sodium hydroxide, lithium hydroxide, or cesium hydroxide in a solvent and stirring, and then acidifying to produce the carboxylic acids of formula (4a): and (4b): or adding the products of Step b) above to an acid mixture and stirring to produce the carboxylic acids of formulas (4a): and (4b): d) contacting the products of Step c) above with an amine in a solvent, and recrystallizing the salt so formed to produce the enriched diastereomer of formula (5): as the amine salt; e) converting the product of Step d) to a carboxylic acid of formula (6): f) adding the product of Step e) to a mixture of iodomethane, a solvent, and a base, and stirring to produce the ester of formula (7): or adding the product of Step e) to methanol and an acid to produce the ester of formula (7): or adding the product of Step e) above to trimethylsilyldiazo-methane and methanol in a solvent to produce the ester of formula (7): or adding the product of Step e) to a solution of diazomethane or trimethylsilyl-diazomethane in a solvent to produce ester of formula (7): g) adding the product of Step f) to a mixture of carbon tetrachloride or ethyl acetate, and acetonitrile, water, sodium periodate, and ruthenium(III) chloride, and stirring to produce the carboxylic acid of formula (8): h) adding the product of Step g) to a mixture of a tertiary amine base, a solvent, and diphenylphosphoryl azide (DPPA), and stirring to produce the isocyanate of formula (9): or adding the product of Step g) above to ethyl chloroformate or isobutyl chloroformate and a base in a solvent at a temperature of from −40° C. to 78° C., followed by adding a solution of sodium azide in water and tetrahydrofuran or acetone, followed by adding toluene or benzene, and refluxing to produce the isocyanate of formula (9): i) adding the product of Step h) to a mixture of a solvent and methanol, and stirring to produce the carbamate of formula (10): j) adding the product of Step i) to a mixture of a solvent and aqueous hydrochloric acid, and stirring to produce a compound of formula (Ia): and k) converting the product of Step j) to a compound of formula (I): and further converting, if desired, to a pharmaceutically acceptable salt by known means.