An improved method with high yield and simple steps for the synthesis of
3-hydroxy-1-acetyladamantane was reported. 3-Hydroxy-1-acetyladamantane is an
important intermediate of Saxagliptin for type 2 diabetes mellitus (T2DM). Its synthetic
method started from 1-adamantanecarboxylic acid via oxidation by sulfuric
acid/nitric acid, then VHA reagent (SOCl2/DMF) and sodium diethyl malonate were
used in one-pot through acylation, substitution, decarboxylation and alkalization to
give the target compound. It is an improved method that VHA reagent (SOCl2/DMF)
was used in the step of acylation which effectively enhanced the total yield up to
74%, and the operations were effectually simplified by the one-pot method. The synthesized
target compound has been characterized by single-crystal X-ray diffraction.
The single-crystal X-ray diffraction analysis demonstrates that the target compound has extensive intermolecular
hydrogen bondings involving the hydroxyl and acetyl groups in the solid state and the
structure of the target compound was proved as 3-hydroxy-1-acetyladamantane.
Keywords: 3-hydroxy-1-acetyladamantane, Saxagliptin, intermediate, one-pot method, single-crystal X-ray diffraction.
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