Method for preparing sitagliptin intermediate via asymmetrical reduction method

Disclosed is a method for synthesizing a sitagliptin intermediate, the method comprising: in the presence of hydrogen and a transition metal catalyst having a chiral phosphine ligand, subjecting a compound of formula II to an asymmetric reductive amination with ammonia or ammonium salt in a proper o...

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Bibliographische Detailangaben
Hauptverfasser: Huang, Luning, Hong, Jian, Gu, Eric, Wang, Boyu, Wang, Yusheng
Format: Patent
Sprache:eng
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Zusammenfassung:Disclosed is a method for synthesizing a sitagliptin intermediate, the method comprising: in the presence of hydrogen and a transition metal catalyst having a chiral phosphine ligand, subjecting a compound of formula II to an asymmetric reductive amination with ammonia or ammonium salt in a proper organic solvent under the condition of adding an acidic additive to produce a compound of formula I, wherein, an R- or S -configuration of a stereocenter is represented by *; the compound of formula I of R configuration can be used to prepare sitagliptin, and a reaction formula is as follows: R 1 and R 2 are each independently selected from hydrogen, C 1 -C 12 linear or branched alkyl, C 3 -C 12 cycloalkyl, C 2 -C 12 alkenyl, C 2 -C 12 alkynyl and C 7 -C 12 arylalkyl. The method has a high yield and a high ee% value, a mild reaction condition and a low production cost, and is simple to operate, convenient to purify, environmental friendly and suitable for industrial production.