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.
Asymmetric synthesis of a high added value chiral amine using immobilized ω-transaminases
Petri, Antonella,Colonna, Valeria,Piccolo, Oreste
, p. 60 - 66 (2019/01/28)
Chiral N-heterocyclic molecules and in particular compounds with an amino functional group such as 3-aminopiperidine are valuable intermediates for the production of a large number of bioactive compounds with pharmacological properties. In this paper, the synthesis of both enantiomers of 3-amino-1-Boc-piperidine by amination of the prochiral precursor 1-Boc-3-piperidone using immobilized ω-transaminases (TAs-IMB), isopropylamine as amine donor and pyridoxal-5’-phosphate (PLP) as cofactor is described. Compared to other methods, the present approach affords the target compound in just one step with high yield and high enantiomeric excess starting from a commercial substrate. The reaction was carried out by using different commercially available immobilized enzymes, evaluating the catalytic activity and the enantioselectivity under different experimental conditions. Re-use of the most efficient enzyme was performed both in batch and in a semi-continuous system. The selected biocatalyst showed good stability under the reaction conditions providing consistent results in terms of conversion and enantiomeric excess after several cycles. The reported results may be of practical interest in view of the development of this sustainable approach to an industrial scale.
