709031-38-9Relevant articles and documents
Biocatalytic ammonolysis of (5S)-4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid, 1-(1,1-dimethylethyl)-5-ethyl ester: Preparation of an intermediate to the dipeptidyl peptidase IV inhibitor Saxagliptin
Gill, Iqbal,Patel, Ramesh
, p. 705 - 709 (2006)
An efficient biocatalytic method has been developed for the conversion of (5S)-4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid, 1-(1,1-dimethylethyl)-5-ethyl ester (1) into the corresponding amide (5S)-5-aminocarbonyl-4,5-dihydro-1H- pyrrole-1-carboxylic acid, 1-(1,1-dimethylethyl)ester (2), which is a critical intermediate in the synthesis of the dipeptidyl peptidase IV (DPP4) inhibitor Saxagliptin (3). (Chemical presented) Candida antartica lipase B mediates ammonolysis of the ester with ammonium carbamate as ammonia donor to yield up to 71% of the amide. The inclusion of Ascarite and calcium chloride as adsorbents for carbon dioxide and ethanol byproducts, respectively, increases the yield to 98%, thereby offering an efficient and practical alternative to chemical routes which yield 57-64%.
(5S)-5-aminocarbonyl-4,5-dihydro-1H-pyrrole-1-carboxylic acid-1(1,1-dimethylethyl)ester preparation method
-
Paragraph 0017; 0018; 0019; 0020; 0021; 0022, (2016/12/01)
The present invention discloses a (5S)-5-aminocarbonyl-4,5-dihydro-1H-pyrrole-1-carboxylic acid-1(1,1-dimethylethyl)ester preparation method, wherein is 4,5-dihydro-1H-pyrrole-1,5-dicarboxylic acid[1-(1,1-dimethylethyl), 5-ethyl]ester is adopted as a raw material, sodium isopropoxide is adopted as an alkali reagent, and the raw material, the alkali reagent and formamide are subjected to a reaction in a solvent so as to obtain the target product. According to the present invention, the reaction conditions in the prior art are further optimized so as to improve the yield and easily achieve industrial production.
An cost-effective and safe process of L-cis-4,5-methanoproline amide, the key synthetic intermediate of saxagliptin, via an improved Simmons-Smith reaction
Ding, Ding,Pan, Xianhua,Yu, Wansheng,Li, Xiaojun,Chen, Suke,Liu, Feng
, p. 719 - 726 (2015/05/05)
L-cis-4,5-Methanoproline amide, a key intermediate of saxagliptin, was synthesized by an improved Simmons-Smith reaction. The zinc carbenoid was formed through Zn/CuBr and CH2I2, under the optimized condition, the title compound was gained with 68% yield and excellent diastereomeric selectivity (40:1 d.r.). The absence of the flammable and expensive ZnEt2 makes this procedure very attractive in large scale production.