Abstract
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.
Highlights
Diabetes, a complex and chronic illness, is becoming a public health problem and even a global societal catastrophe
According to the figures displayed in the 8th edition of the Diabetes Atlas issued by the International Diabetes Federation, until 2017, there were about 451 million adults who lived with diabetes all over the world, and this number may rise to 693 million in 2045, if nothing is done [1]
Rough retrosynthesis analysis, we found that (S)-NBoc-3-hydroxyadamantylglycine is a key intermediate of Saxagliptin [7], and it can be prepared economically and efficiently from 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (I) by asymmetric reductive amination [8, 9] (Figure 1)
Summary
A complex and chronic illness, is becoming a public health problem and even a global societal catastrophe. Rough retrosynthesis analysis, we found that (S)-NBoc-3-hydroxyadamantylglycine is a key intermediate of Saxagliptin [7], and it can be prepared economically and efficiently from 2-(3-hydroxy-1-adamantyl)-2-oxoacetic acid (I) by asymmetric reductive amination [8, 9] (Figure 1). Politino et al [10] originally describe a method treating 1-bromoadamantane as starting material, which reacted with silane coupling agent to give α hydroxy acid and through esterification, Swern oxidation, hydroxylation, and hydrolysis to produce the target compound I. Henryon et al [11] developed an improved route to start with 1-adamantanecarboxylic acid, which was acylated by thionyl chloride (SOCl2) and substituted by cyanide reagent TMSCN to afford cyanide and underwent hydrolysis, esterification, and hydroxylation to obtain the intermediate. It was found that this route demanded greatly multiple procedures as well as relatively complex
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