709031-29-8Relevant articles and documents
A facile synthesis of saxagliptin intermediate N-Boc-3-hydroxyadamantylglycine
Chen, Yingjie,Wang, Anmin,Tao, Zhu,Deng, Yu,Hu, Xiangnan
, p. 4113 - 4121 (2015)
Commercial-scale synthesis of (S)-N-Boc-3-hydroxyadamantylglycine (I), which is the key intermediate of saxagliptin, can be achieved from 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (6) by reductive amination with phenylalanine dehydrogenase. The biological enzyme used in the original medicinal chemistry route is expensive and not easily obtained, making it unsuitable for further development. In this work, we developed a conventional chemical approach to give the corresponding oxime from oxoacetic acid followed by reduction of oxime and protected amino with (Boc)2O to afford the racemic mixture of N-Boc-3-hydroxyadamantylglycine (III). Utilizing this route, N-Boc-3-hydroxyadamantylglycine was prepared in six linear chemical steps with 38 % overall yield.
Synthetic method of saxagliptin intermediate (by machine translation)
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Paragraph 0041-0043, (2020/11/23)
(1) The compound 1 is reacted under the action of sodium ethoxide in a substitution reaction under the action of sodium ethoxide to form compound 2 by stirring and refluxing 2 under the action of sodium ethoxide to form compound 2; (8 hours) compound 3 is reacted 3 at room temperature under the alkaline condition by adding L - arginine to obtain a salvildagliptin intermediate, compound 3) and liquid bromine under the action of sodium ethoxide and then adding L-arginine under the action of sodium ethoxide under the action of sodium ethoxide and then 8 hours adding L-arginine 4 under the 4 action of 4 sodium ethoxide 12 hours. Raw materials and reagents are cheap and easily available, the reaction operation is simple, the reaction conditions are mild, the yield is high, the quality is good, the resolution end product can reach 99% ee values, and the requirements of drug intermediates are met. (by machine translation)
Intermediates for synthesizing sand Geleg sandbank N-tert-butoxycarbonyl-3-hydroxy-1-adamantyl-D-gly method
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Paragraph 0014; 0024; 0025; 0027, (2018/02/04)
The invention discloses a novel method of preparing an important saxagliptin intermediate N-t-butyloxycarboryl-3-hydroxyl-1-adamantyl-D-glycine. The method comprises the following steps: S1, carrying out an asymmetric reduction amination reaction on 2-(3-hydroxyl-1-adamantyl)-2-oxo-tert-butyl acetate and benzylamine under the effect of a self-made chiral acylamino alcohol catalyst, and hydrolyzing ester to obtain 3-hydroxyl-1-adamantyl-D-glycine; and S2, carrying out a reaction on 3-hydroxyl-1-adamantyl-D-glycine and di-tert-butyl dicarbonate ester to obtain N-t-butyloxycarboryl-3-hydroxyl-1-adamantyl-D-glycine. The synthetic method of the important saxagliptin intermediate N-t-butyloxycarboryl-3-hydroxyl-1-adamantyl-D-glycine provided by the invention is low in cost and available in raw materials, short in step, mild in reaction condition, simple and convenient to operate, high in synthetic efficiency, environment-friendly and suitable for industrialized production, and provides a novel path for preparing saxagliptin and intermediates thereof.
