Abstract: A process is disclosed for preparation of piperidine derivatives, preferably 1,3-dioxolo [4,5-c] piperidin-7-ols such as (3aS, 4R, 7S, 7aR)-2,2,4-trimethyl-1,3-dioxolo [4,5-c] piperidin-7-ol and its polyhydroxylated derivatives. In a preferred process, 2,3-O-isopropylidene-1,4-lactone (A) is reacted with methanesulfonyl chloride to form (3aR, 4S, 6aR) methanesulfonic acid 2,2-dimethyl-6-oxo-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl (B). Compound (B) is then reacted with methylmagnesium halide to form (3aR, 4S, 6aR)-methanesulfonic acid 6-hydroxy-2,2,6-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl ester (C), which is reacted with phthalimide to form (3aR, 4S, 6aR)-2-(6-hydroxy-2,2,6-trimethyl-tetrahydro-furo[3,4-d][1,3]dioxol-4-ylmethyl)-isoindole-1,3-dione (D). Compound (D) is reacted with hydrazine to form (3S, 7S, 7aR)-2,2,4-trimethyl-3a,6,7,7a-tetrahydro-[1,3]dioxolo[4,5-c]pyridin-7-ol (E), which is hydrogenated to give the corresponding 1,3-dioxolo [4,5-c] piperidin-7-ol (F).

Abstract: A process for the preparation of highly pure 1-(mercaptomethyl)-cyclopropaneacetic acid is described. Treatment of 1-(hydroxymethyl)-cyclopropaneacetonitrile with an acid provides the corresponding imino ester and/or halo-amide, which when reacted with thiourea provide the corresponding amide-isothiuronium salt. Hydrolysis of the amide-isothiuronium salt followed by an in situ oxidation allows the facile isolation and purification of 1-[1 -(carboxymethyl)-cyclopropanemethyldisulfanylmethyl]-cyclopropaneacetic acid (also known as 1-(mercaptomethyl)-cyclopropaneacetic acid disulfide). Reduction of the 1-(mercaptomethyl)-cyclopropaneacetic acid disulfide under mild conditions provides the 1-(mercaptomethyl)-cyclopropaneacetic acid with high purity.