Publication number: 20050176752
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).
Type:
Application
Filed:
January 7, 2005
Publication date:
August 11, 2005
Inventors:
Jean-Francois Meunier, Herika Marrugo, Gregory Bydlinski