334618-23-4Relevant articles and documents
Preparation of (R)-3-aminopiperidine by resolution with optically active cyclic phosphoric acids
Sun, Yujuan,Hu, Beibei,Jing, Yongshuai,Wu, Jialiang,Zhou, Maochao,Chen, Meng,Hao, Feifei,Zhang, Chen,Sun, Fengxia
, p. 379 - 384 (2021)
(R)-3-aminopiperidine ((R)-APD), a key intermediate for alogliptin, trelagliptin, and linagliptin, was successfully resolved from racemic 3-aminopiperidine with an enantiomerically pure resolving agent, namely, (R)-4-(2-chlohydroxy-1.3.2-dioxaphosphorinane 2-oxide ((R)-CPA), via diastereomeric salt formation. By this resolution approach, (R)-3-aminopiperidine was obtained in 99.5% yield with 99.6%e.e.
Preparation method and application of (R)-3-aminopiperidine dihydrochloride
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, (2020/12/08)
The invention provides a preparation method and application of (R)-3-aminopiperidine dihydrochloride. The preparation method comprises the following steps: obtaining (S)-1, 5-dichloro-2-pentanol through the reaction of (S)-epichlorohydrin and 2-chloroethyl magnesium bromide; carrying out an intramolecular cyclization reaction in the presence of an alkaline substance to generate (S)-5-chloro-1, 2-epoxypentane; enabling the (S)-1-benzylamino-5-chloro-2-epoxypentane to react with benzylamine to generate (S)-1-benzylamino-5-chloro-2-pentanol; then obtaining (S)-1-benzyl-3-hydroxypiperidine throughan intramolecular ring closing reaction of (S)-1-benzylamino-5-chloro-2-pentanol; continuing to react with the sulfonyl chloride compound to obtain (R)-1-benzyl-3-sulfonyloxy piperidine; further reacting with benzylamine to obtain (R)-1-benzyl-3-benzylamino piperidine; and finally, under the action of a palladium catalyst, removing benzyl through hydrogenation, thus obtaining the product (R)-3-aminopiperidine dihydrochloride. The preparation method has the advantages of few side reactions, high yield, good product quality, convenient purification, easily available raw materials, low price, mild reaction conditions, high safety, environmental protection, simplicity, practicality, and suitableness for industrial batch production.
Synthesis method of chiral 3-aminopiperidine and derivatives of 3-aminopiperidine
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, (2019/09/17)
The invention relates to a synthesis method of chiral 3-aminopiperidine and derivatives of 3-aminopiperidine. According to the synthesis method, R (or S)-piperidine-3-ethyl formate-L (or D)-tartrate is subjected to a hydrazinolysis reaction after being subjected to benzyl protection, and R or S-1-benzyl-3-aminopiperidine is obtained through azidation and Curtius rearrangement. R or S-1-benzyl-3-aminopiperidine is subjected to debenzylation, R or S-3-aminopiperidine can be obtained, R or S-1-benzyl-3-aminopiperidine is subjected to 3-t-butyloxycarboryl protection and debenzylation in sequence,R or S-(3-t-butyloxycarborylamino) piperidine can be obtained, and corresponding salts of R or S-3-aminopiperidine can be obtained through hydrolyzing deprotection of R or S-(3-t-butyloxycarborylamino) piperidine under the acidic condition. The synthesis method of chiral 3-aminopiperidine and the derivatives of 3-aminopiperidine is low in cost, facilitates industrialization and has high optical purity.
