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1. (WO2005066181) PROCESS FOR THE PREPARATION OF 1,3-DIOXOLO [4,5-C] PIPERIDIN-7-OLS AND RELATED COMPOUNDS
Latest bibliographic data on file with the International Bureau   

Pub. No.:    WO/2005/066181    International Application No.:    PCT/CA2005/000013
Publication Date: 21.07.2005 International Filing Date: 06.01.2005
IPC:
A61K 31/4355 (2006.01), A61K 31/4741 (2006.01), A61P 31/12 (2006.01), C07D 211/40 (2006.01), C07D 491/02 (2006.01), C07D 491/056 (2006.01)
Applicants: DELMAR CHEMICALS INC. [CA/CA]; 9321 Rue Airlie, LaSalle, Québec H8R 2B2 (CA) (For All Designated States Except US).
MEUNIER, Jean-Francois [CA/CA]; (CA) (For US Only).
MARRUGO, Herika [CA/CA]; (CA) (For US Only).
BYDLINSKI, Gregory [CA/CA]; (CA) (For US Only)
Inventors: MEUNIER, Jean-Francois; (CA).
MARRUGO, Herika; (CA).
BYDLINSKI, Gregory; (CA)
Agent: JOACHIM, Roland, H.; RIDOUT & MAYBEE LLP, One Queen Street East, Suite 2400, Toronto, Ontario M5C 3B1 (CA)
Priority Data:
2,455,018 09.01.2004 CA
Title (EN) PROCESS FOR THE PREPARATION OF 1,3-DIOXOLO [4,5-C] PIPERIDIN-7-OLS AND RELATED COMPOUNDS
(FR) PROCEDE DE PREPARATION DE 1,3-DIOXOLO [4,5-C] PIPERIDIN-7-OLS ET COMPOSES CONNEXES
Abstract: front page image
(EN)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). The synthesis has an overall yield which is typically greater than 50% and avoids the use of reagents such as triflic anhydride and sodium azide.
(FR)L'invention porte sur un procédé de préparation de dérivés de pipéridine, de préférence 1,3-dioxolo [4,5-c] pipéridin-7-ols tels que (3aS, 4R, 7S, 7aR)-2,2,4-triméthyl-1,3-dioxolo [4,5-c] pipéridin-7-ol et leurs dérivés polyhydroxylés. Selon un procédé préféré, 2,3-O-isopropylidène-1,4-lactone (A) est mis à réagir avec un chlorure de méthanesulfonyl de façon à obtenir un acide (3aR, 4S, 6aR) méthanesulfonique 2,2-diméthyl-6-oxo-tétrahydro-furo[3,4-d][1,3] dioxol-4-ylméthyl (B). Le composé (B) est ensuite mis à réagir avec un halogénure de méthylmagnésium afin d'obtenir un acide (3aR, 4S, 6aR)-méthanesulfonique 6-hydroxy-2,2,6-triméthyl-tétrahydro-furo[3,4-d][1,3]dioxol-4-ylméthyl ester (C), lequel est mis à réagir avec phtalimide de façon à obtenir (3aR, 4S, 6aR)-2-(6-hydroxy-2,2,6-triméthyl-tétrahydro-furo[3,4-d][1,3]dioxol-4-ylméthyl)-isoindole-1,3-dione (D). Le composé (D) est mis à réagir avec hydrazine de façon à obtenir (3S, 7S, 7aR)-2,2,4-triméthyl-3a,6,7,7a-tétrahydro-[1,3]dioxolo[4,5-c]pyridin-7-ol (E), lequel est hydrogéné pour donner 1,3-dioxolo[4,5-c]piperidin-7-ol (F) correspondant. La synthèse a un rendement global généralement supérieur à 50 % et évite d'utiliser des réactifs tels que l'anhydride triflique et l'azide de sodium.
Designated States: AE, AG, AL, AM, AT, AU, AZ, BA, BB, BG, BR, BW, BY, BZ, CA, CH, CN, CO, CR, CU, CZ, DE, DK, DM, DZ, EC, EE, EG, ES, FI, GB, GD, GE, GH, GM, HR, HU, ID, IL, IN, IS, JP, KE, KG, KP, KR, KZ, LC, LK, LR, LS, LT, LU, LV, MA, MD, MG, MK, MN, MW, MX, MZ, NA, NI, NO, NZ, OM, PG, PH, PL, PT, RO, RU, SC, SD, SE, SG, SK, SL, SM, SY, TJ, TM, TN, TR, TT, TZ, UA, UG, US, UZ, VC, VN, YU, ZA, ZM, ZW.
African Regional Intellectual Property Organization (BW, GH, GM, KE, LS, MW, MZ, NA, SD, SL, SZ, TZ, UG, ZM, ZW)
Eurasian Patent Organization (AM, AZ, BY, KG, KZ, MD, RU, TJ, TM)
European Patent Office (AT, BE, BG, CH, CY, CZ, DE, DK, EE, ES, FI, FR, GB, GR, HU, IE, IS, IT, LT, LU, MC, NL, PL, PT, RO, SE, SI, SK, TR)
African Intellectual Property Organization (BF, BJ, CF, CG, CI, CM, GA, GN, GQ, GW, ML, MR, NE, SN, TD, TG).
Publication Language: English (EN)
Filing Language: English (EN)