- Method for synthesizing sitagliptin intermediate
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The invention relates to a method for synthesizing a sitagliptin intermediate. The method is characterized in that asymmetric reduction ammonification of a compound of formula II and ammonia or ammonium salt in the presence of a chiral phosphorus coordinated transition metal catalyst in an appropriate organic solvent containing an acidic additive to obtain a compound of formula I. The R- or S- configuration of a stereocenter is represented by *, and the formula I with the R configuration can be used to prepare sitagliptin. A reaction equation is shown in the description; and R and R in the reaction equation are respectively independently selected from hydrogen, C1-C12 linear or branched alkyl groups, C3-C12 cycloalkyl groups, C2-C12 alkene groups, C2-C12 alkynyl groups and C7-C12 arylalkyl groups. The method has the advantages of high yield and ee% value, mild reaction conditions, simple operation, convenient purification, low production cost, environmental protection, and suitableness for industrial production.
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Paragraph 0054; 0055; 0056
(2016/10/24)
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- Substrate screening of amino transaminase for the synthesis of a sitagliptin intermediate
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We reported herein a new enzymatic route to synthesize a sitagliptin intermediate using an aminotransferase. Substrate profile indicated that hydroxyethyl-3-oxo-4-(2,4,5-trifluorophenyl)butanoate, among 11 analogs, showed the best biocatalytic performance, partially due to its best solubility in the enzymatic system. The corresponding amino esters showing strong product inhibition on the reaction, were inclined to autohydrolyze, thus driving the reaction forward, which indicated the contribution of the rapid hydrolysis of hydroxyethyl ester to the biocatalytic performance. The reaction was performed at 100?mM with 82% conversion in 24?h. The amino ester product was further transformed to Boc-(R)-3-amino-4-(2,4,5-trifluorophenyl)butyric acid, the key intermediate of sitagliptin.
- Hou, Anwei,Deng, Zixin,Ma, Hongmin,Liu, Tiangang
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supporting information
p. 4660 - 4664
(2016/07/15)
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- PREPARATION OF SITAGLIPTIN INTERMEDIATES
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The invention relates to the preparation of chiral compounds, in particular to the preparation of chiral compounds which may be used as intermediates for the preparation of anti-diabetic agents, preferably sitagliptin.
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- Preparation of sitagliptin intermediates
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The invention relates to the preparation of chiral compounds, in particular to the preparation of chiral compounds which may be used as intermediates for the preparation of anti-diabetic agents, preferably sitagliptin.
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- SITAGLIPTIN SYNTHESIS
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The present invention relates to novel processes for the preparation of enantiomerically enriched β-amino acid derivatives such as β-amino esters useful for the synthesis of enantiomerically enriched biologically active molecules such as sitagliptin. The key step involves the resolution of the racemate with mandelic acid.
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- SITAGLIPTIN SYNTHESIS
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The present invention relates to novel processes for the preparation of enantiomerically enriched β -amino acid derivatives such as β -amino esters useful for the synthesis of enantiomerically enriched biologically active molecules such as sitagliptin. The key step involves the resolution of the racemate with mandelic acid.
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Page/Page column 27
(2010/12/17)
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- PROCESS FOR THE PREPARATION OF SITAGLIPTIN AND ITS INTERMEDIATES
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The present invention relates to novel and improved processes for the preparation of Sitagliptin compound of formula (1) and its intermediates.
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Page/Page column 44
(2010/11/05)
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