709031-28-7Relevant articles and documents
Method for preparing non-natural amino acid
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, (2020/09/18)
The invention relates to a preparation and chiral resolution method for unnatural amino acids. The method comprises the following steps: with adamantanecarboxylic acid as a raw material, preparing 3-hydroxy-adamantanecarboxylic acid; carrying out chlorination, oxidation and the like so as to obtain 2-(3-hydroxy-1-adamantyl)glyoxalic acid; reacting 2-(3-hydroxy-1-adamantyl)glyoxalic acid with hydroxylamine hydrochloride so as to obtain 3-hydroxyadamantyl-glyoxalic acid oxime; carrying out reduction with a reducing agent and protection with Boc acid anhydride so as to obtain N-tertbutyloxycarbonyl-3-hydroxyadamantylglycine; and carrying out resolution with organic base so as to obtain two unnatural amino acids, i.e., (S)-N-tertbutyloxycarbonyl-3-hydroxyadamantylglycine and (R)-N-tertbutyloxycarbonyl-3-hydroxyadamantylglycine. Compared with the prior art, the method provided by the invention has the following advantages: improved synthesis technology; mild reaction conditions; small environmental pollution; and applicability to industrial production.
An Efficient and Practical Method for the Synthesis of Saxagliptin Intermediate 2-(3-Hydroxy-1-adamantane)-2-oxoacetic Acid and Its Optimization
Liao, Qi,Jiang, Lan,Li, Cong,Shen, Yaling,Wang, Min,Cao, Chengkun,Hu, Xiangnan
, (2019/11/05)
A mild and relatively simple way for preparation of 2-(3-hydroxy-1-adamantane)-2-oxoacetic acid (I) was reported. It was prepared from 1-adamantanecarboxylic acid (II) via sulfuric acid/nitric acid to get 3-hydroxy-1-adamantanecarboxylic acid (III); treated with the one-pot method through acylation, condensation, and decarboxylation to obtain 3-hydroxy-1-acetyladamantane (IV); and finally oxidized by potassium permanganate (KMnO4) to get the target compound (I). The overall yield was about 60%, which provides a new idea for commercial production of saxagliptin intermediate.
PROCESS FOR PREPARING DIPEPTIDYL PEPTIDASE IV INHIBITORS AND INTERMEDIATES THEREFOR
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, (2016/07/27)
A process for preparing an amine of the structure which comprises a. treating an aqueous solution of a keto acid of the structure with ammonium formate, nicotinamide adenine dinucleotide, dithiothreitol and partially purified phenylalanine dehydrogenase and/or formate dehydrogenase enzyme (PDH/FDH); and b. adjusting pH of the reaction mixture with sodium hydroxide to form the desired amine which is substantially free of undesirable excess ammonium ions.
A facile and economic method for the synthesis of (S)-N-Boc-3′-hydroxyadamantylglycine
Li, Jie,Jiang, Xue,Gan, Run,Zhang, Ming,Pan, Xinmei,Hu, Xiangnan
, p. 5709 - 5721 (2016/06/01)
(S)-N-Boc-3′-hydroxyadamantylglycine (I) is an important intermediate of saxagliptin for type 2 diabetes mellitus (T2DM). It was prepared from 1-adamantanecarboxylic acid(1) via mild reaction with sulfuric acid/nitric acid, VHA reagent (SOCl2/DMF) and sodium diethyl malonate, then was treated with hydrolysis, decarboxylation, alkalization and oxidation to give 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (4), then through oximation, reduction and (Boc)2O protection to give the N-Boc-3′-hydroxyadamantylglycine(6), then was treated with quinidine to get (S)- N-Boc-3′-hydroxyadamantylglycine(I) and quinine to get (R)–N-Boc-3′-hydroxyadamantylglycine(II). Finally, Compound II was racemized by dicyclohexylcarbodiimide (DCC) and sodium?hydride (NaH) to afford compound 6. In this route, the overall yield of preparing compound I was about 35?% and the enantiomeric excess (ee) reach to 99?%. This route provided a novel idea for the preparation of (S)-N-Boc-3′-hydroxyadamantylglycine.
Preparation method of saxagliptin intermediate (A1)
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Paragraph 0019; 0024, (2017/02/24)
The invention discloses a preparation method of a saxagliptin intermediate (A1), and belongs to the field of chemical pharmacy. Adamantyloxoacetic acid is obtained through a Grignard reaction, hydrolysis and a mixed acid reaction with bromoadamantane as an initial raw material. The method has the advantages of simple and easy operation, high yield, small pollution, and suitableness for industrial production.
A novel method for the synthesis of 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid
Pan, Xianhua,Lu, Qingling,Li, Xiaojun,Zhang, Jianshui,Yu, Wansheng,Liu, Feng
, p. 722 - 723 (2014/01/23)
A simple and efficient synthetic route to 2-(3-hydroxy-1-adamantyl)-2- oxoacetic acid is described by a direct oxidation reaction of adamantan-1-yl-ethan-1-one which could be prepared by a Grignard reaction. In this approach, the oxidation reaction introduced the hydroxyl and carboxyl group by a one-pot reaction.
Biocatalytic asymmetric synthesis of unnatural amino acids through the cascade transfer of amino groups from primary amines onto keto acids
Park, Eul-Soo,Dong, Joo-Young,Shin, Jong-Shik
, p. 3538 - 3542 (2014/01/06)
Flee to the hills: An unfavorable equilibrium in the amino group transfer between amino acids and keto acids catalyzed by α-transaminases was successfully overcome by coupling with a ω-transaminase reaction as an equilibrium shifter, leading to efficient asymmetric synthesis of diverse unnatural amino acids, including L-tert-leucine and D-phenylglycine. Copyright
Preparation of 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid: A key intermediate for saxagliptin
Li, Jingke,Zhang, Shurong,Zhou, Hongrui,Peng, Jun,Feng, Yue,Hu, Xiangnan
experimental part, p. 347 - 350 (2012/09/08)
An optimized synthetic approach to prepare 2-(3-hydroxy-1-adamantyl)-2- oxoacetic acid has been reported in a good yield under mild experimental conditions. It was synthesized from 1-adamantanecarboxylic acid via successful reaction with thionyl chloride and sodium diethyl malonate to give dimethyl (1-adamantylcarbonyl) malonate, which was subjected to hydrolysis and decarboxylation by a mixture of acetic acid with water and sulfuric acid and then oxidation by potassium permanganate. The synthesized adamantane derivative was utilized to saxagliptin.
PROCESS FOR THE PREPARATION OF ADAMANTANE DERIVATIVES
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Page/Page column 7, (2008/06/13)
The invention relates to a process for the preparation of 3-hydroxyadamantaneglyoxylic acid of the general formula (1) or a derivative or salt thereof. In the process, an 1-acyl derivative of adamantane having the formula (2): wherein R is a C1-C5 hydrocarbyl; CH2OH; CHO; COOH, is contacted with an oxidant under oxidizing conditions leading to the 3-hydroxyadamantaneglyoxylic acid (1) or the derivative or salt thereof.
Process for the preparation of adamantane derivatives
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Page/Page column 3, (2008/06/13)
The invention relates to a process for the preparation of 3-hydroxyadamantaneglyoxylic acid of the general formula (1) or a derivative or salt thereof. In the process, an 1-acyl derivative of adamantane having the formula (2): wherein R is a C1-C5 hydrocarbyl; CH2OH; CHO; COOH, is contacted with an oxidant under oxidizing conditions leading to the 3-hydroxyadamantaneglyoxylic acid (1) or the derivative or salt thereof.
