- PROCESS FOR MAKING AZETIDINE-3-CARBOXYLIC ACID
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The present invention is directed to an improved process for synthesizing azetidine-3-carboxylic acid, comprising triflating diethylbis(hydroxymethyl)malonate followed by azetidine ring-formation by intramolecular cyclization using an amine, decarboxylation to give the mono acid azetidine and hydrogenation to give the title compound. Azetidine-3-carboxylic acid is useful as an intermediate for making certain S1P?1#191/Edg1 receptor agonists, which are immunosupressive agents.
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- Process for preparing azetidine derivatives; and intermediates therein
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Process for the preparation of a compound of formula or a salt thereof STR1 wherein R1 represents a hydrogen atom or a group of formula R2 SO2 or phenyl--CH(R3)--wherein R2 represents a phenyl, tolyl or C1-4 alkyl group and R3 represents a hydrogen atom or a phenyl of C1-4 alkyl group, which process comprises contacting nickel in an oxidation state of at least 3 with a 3-hydroxymethyl azetidine derivative of formula STR2 wherein R4 represents a group of formula R2 SO2 or phenyl--CH(R3)--and R5 represents a hydrogen atom or a hydroxymethyl group or a group of formula COOH or a salt thereof, followed, where R5 is not a hydrogen atom, by the decarboxylation of the compound of the 3,3-dicarboxylic intermediate product or a salt thereof and, if desired to produce a compound in which R1 represents a hydrogen atom, by deprotection of the N-atom. Also, novel N-substituted azetidine carboxylate derivatives of the formula STR3 wherein X represents a group CH2 OH or COOY where Y represents a hydrogen or an alkali or alkaline earth metal atom.
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