Water → (3R)-4-{[(1R)-2-methyl-1-(2-methylpropanoyloxy)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid

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Reaction Steps

In certain embodiments, crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxyl)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid hemihydrate (1b) can be prepared by steps comprising providing a first solution comprising 1-((2,5-dioxopyrrolidin-1-yl-oxycarbonyloxy)-2-methylpropyl-2-methylpropanoate (3) prepared as a racemic mixture, (R)-baclofen (2), about 65% v/v water and about 35% v/v methyl tert-butyl ether; increasing the temperature of the first solution to create a second solution comprising (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxyl)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid (1) and (3R)-4-{[(1R)-2-methyl-1-(2-methylpropanoyloxyl)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid (4); and decreasing the temperature of the second solution to provide crystalline (3R)-4-{[(1S)-2-methyl-1-(2-methylpropanoyloxyl)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid hemihydrate (1b) and (3R)-4-{[(1R)-2-methyl-1-(2-methylpropanoyloxyl)propoxy]carbonylamino}-3-(4-chlorophenyl)butanoic acid (4).

Provenance & Evidence