Stereospecific substitution of enantiomerically pure 1-(2-pyridinyl)ethyl methanesulfonate with β-dicarbony compounds

Abstract

The alkylation of the sodium salt of the malonic acid diester with (R)-1-(2-pyridinyl)ethyl methanesulfonate (2) gave the dimethyl (R)-[1-(2-pyridinyl)ethyl]malonate (3a), stereospecifically. The alkylation reaction of methyl acetoacetate gave the methyl (2′S,2R/2S)-3-oxo-2-[1-(2- pyridinyl)ethyl]butanoate (3d) along with the methyl (S)-3-[1-(2-pyridinyl) ethoxy]-2-butenoate (4d). The acid hydrolysis and decarboxylation of 3d under acidic conditions gave (R)-4-(2-pyridinyl)pentan-2-one (6), and the alkylation of methyl (R)-[1-(2-pyridinyl)ethyl]acetoacetate with benzyl bromide gave a mixture of C-benzylated and O-benzylated products 7 and 8. © 2002 Pharmaceutical Society of Japan.