- A practical process for the preparation of azetidine-3-carboxylic acid
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A practical and convenient synthesis of azetidine-3-carboxylic acid (1) that proceeded in 55% overall yield from commercially available diethylbis(hydroxymethyl)malonate (3) is reported. Azetidine ring-formation was achieved in high yield by cyclization of bistrifiate of the diol (3) and benzylamine. Decarboxylation under carefully pH-controlled conditions gave the mono acid azetidine that was hydrogenated to give the title compound.
- Miller, Ross A.,Lang, Fengrui,Marcune, Benjamin,Zewge, Daniel,Song, Zhiguo J.,Karady, Sandor
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- Method for synthesizing azetidine -3 - formic acid
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The invention relates to the field of organic synthesis and particularly relates to a synthetic method of azetidine-3-formic acid. The synthetic method comprises the following steps of adopting 2,2-bis(hydroxymethyl)malonic acid-1,3-diethyl ester to react with benzhydrylamine after protection of methylsulfonyl chloride, and then by decarboxylation and diphenylmethyl-removing protection, obtaininga final product, namely the azetidine-3-formic acid. The synthetic method has the advantages that the 2,2-bis(hydroxymethyl)malonic acid-1,3-diethyl ester is adopted as a raw material, and is cheap and easy to obtain; compared with the original synthesis route, the cost of the whole synthesis route is reduced by 30% or more, and a highly-toxic substance (sodium cyanide) is not adopted, so that theindustrial production prospect is great.
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Paragraph 0029-0030
(2021/10/02)
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- Production methods of nitrogen heterocyclic carboxylic acid intermediate and 3-azetidine carboxylic acid
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The invention discloses production methods of a nitrogen heterocyclic carboxylic acid intermediate and 3-azetidine carboxylic acid, and relates to the technical field of pharmaceutical and chemical industry. The production method of the nitrogen heterocyclic carboxylic acid intermediate used for producing the 3-azetidine carboxylic acid comprises the steps of mixing a nitrogen heterocyclic compound and a Wittig reaction agent, carrying out a Wittig reaction, and conducting separation to obtain a nitrogen heterocyclic formaldehyde intermediate; and subjecting the nitrogen heterocyclic formaldehyde intermediate to an oxidation reaction, and conducting separation to obtain the nitrogen heterocyclic carboxylic acid intermediate, wherein the nitrogen heterocyclic compound is selected from at least one of 1-benzhydrylazetidin-3-one, 1-benzylazetidin-3-one, 1-Boc-3-azetidinone and 1-acetylazetidin-3-one. According to the production method of the 3-azetidine carboxylic acid, the nitrogen heterocyclic carboxylic acid intermediate is subjected to hydrogenolysis, a production cycle is short, a production process is safe and reliable, the production cost is low, the purity is higher than 98%,and the yield can reach 82.8%.
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Paragraph 0084-0087; 0102-0103
(2019/11/20)
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- 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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- Catalytic hydrogenolysis
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Preparation of azetidine-3-carboxylic acid or a salt thereof from N-benzylazetidine-3-carboxylic acid or a salt thereof by catalytically hydrogenating the N-benzylazetidine-3-carboxylic compound in the presence of water, formate ions, and ammonium and/or alkylammonium ions. Novel ammonium and alkylammonium salts are claimed.
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- Azetidine-3-carboxylic acid derivatives
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The novel ester, N-benzylazetidine-3-carboxylic acid methyl ester and its use in the preparation of the corresponding free acid by a process which comprises reacting N-benzyl-3-cyanozetidine with methanol and hydrolyzing the resulting methyl ester with hot water.
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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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- Method for sterilizing male parts of plants
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3-Carboxyazetidine or a hydrate, salt or lower alkyl ester thereof is used to sterilize male parts of plants.
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- Process for preparing azetidine derivatives and intermediates thereof
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The invention provides a process for preparing azetidine-3-carboxylic acid or salts thereof; useful as chemical hybridizing agents, which comprises treating a compound of the formula STR1 wherein R represents a hydrogen atom or a group of formula R1 R2 CH-- wherein R1 and R2 are independently selected from hydrogen, alkyl or optionally substituted phenyl moieties, with nitric acid and subjecting the resulting initial product to acid conditions to produce an acid-addition salt of azetidine-3-carboxylic acid, and thereafter, if desired, converting the acid-addition salt to the free acid or another salt of the acid, 1-nitrosoazetidine-3,3-dicarboxylic acid, 1-nitrosoazetidine-3-carboxylic acid and salts thereof being intermediates in the process.
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- Preparation of 1-benzylazetidine-3-ol derivatives
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A process for the preparation of 1-substituted azetidin-3-ol derivatives of the formula: STR1 in which R1 represents a hydrogen atom or an alkyl, aryl or aralkyl group in which the alkyl moiety contains up to eight carbon atoms, by cyclizing a solution in triethylamine of an aminoalcohol of the formula: STR2 in which Hal represents a halogen atom and the use of such derivatives as intermediates for the preparation of azetidine-3-carboxylic acid derivatives.
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- A process for the preparation of an azetidine-3-carboxylic acid or salt thereof
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The invention relates to a process for the preparation of an azetidine-3-carboxylic acid of the formula I: or a salt thereof, wherein R1 represents a hydrogen atom, a C1-6alkyl or C3-8cycloalkyl group or a group phenyl-CH(R3)- wherein R3 represents a hydrogen atom, a phenyl or an alkyl group of 1-4 carbon atoms, which process comprises reacting an azetidine of the formula II: wherein R1 has the meanings defined above, and X represents a hydrogen atom, a carboxyl or a group, with an alkali metal base at a temperature of from 150 to 300°C in the presence of a catalyst comprising a metal of the Group IIB of the Periodic System and/or a compound of said metal, and if desired converting the obtained azetidine-3-carboxylic acid salt into the corresponding acid; and to novel alkali, alkaline earth and quaternary ammonium salts of such acids.
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- Arylsulphonyl azetidine compounds, their preparation and their use as intermediates
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Azetidine compounds of the general formula I STR1 wherein Ar represents a para-tolyl group and X represents a hydrogen atom, a carboxyl group or a hydroxymethyl group; their preparation from pentaerythritol via compounds of formula STR2 or two hydroxyl groups and Z represents Hal or OH, together with their use as intermediates in the preparation of 3-carboxyazetidine; also the compounds of formula STR3 wherein R1 and R2 both represent hydrogen, or together represent STR4 The compounds are intermediates for a known chemical hybridizing agent.
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- Preparation of 1-benzylazetidin-3-ol
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1-Benzylazetidin-3-ol, a precursor to 3-carboxyazetidine, is prepared by heating N-benzyl-3-amino-1-chloropropan-2-ol in an aqueous medium, optionally treating the resulting hydrochloride salt with an alkali metal base.
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- Method for sterilizing male parts of plants
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3-Carboxyazetidine or a hydrate, salt or lower alkyl ester thereof is used to sterilize male parts of plants.
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