Novel preparation method for butyrolactone derivative

Abstract

The invention discloses a novel preparation method for a butyrolactone derivative. The method includes the steps of: (1) reacting pentanoic acid shown as formula (II) with ethyl bromoacetate under theaction of lithium diisopropylamide to obtain a compound shown as formula (III); (2) splitting the compound shown as formula (III) with chiral phenylethylamine to obtain a compound shown as formula (IV); (3) subjecting the compound shown as formula (IV) to reduction of carboxyl by borane so as to obtain a compound shown as formula (V); and (4) carrying out cyclization reaction on the compound shown as formula (V) to obtain a butyrolactone derivative shown as formula (I). The brand new butyrolactone derivative synthesis method provided by the invention has the advantages of low cost of synthetic raw material pentanoic acid, need of just 4-step reaction, and good stereoselectivity, and can obviously reduce the production cost. And the synthesis route is shown as the specification.

Description

technical field [0001] The invention relates to the technical field of organic compound synthesis, and more specifically relates to a novel method for preparing butyrolactone derivatives. Background technique [0002] The butyrolactone derivative represented by the following formula (I) is a key intermediate in the synthesis of the novel antiepileptic drug Brivaracetam. [0003] [0004] At present, many documents have reported the synthesis method of the above-mentioned butyrolactone derivatives. For example, the following synthesis method has been reported in the patent document WO2016 / 191435, wherein R-epichlorohydrin is used as raw material, and diethyl malonate Ester condensation, reaction with ethyl magnesium bromide, and finally decarboxylation to obtain the key intermediate butyrolactone derivatives, but the cost is relatively expensive. [0005] [0006] As another example, the document Hughes, G. et al., J.Am.Chem.Soc.2003, 125, 11253-11258 reported that n-v...

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Problems solved by technology

[0006] As another example, the document Hughes, G. et al., J.Am.Chem.Soc.2003, 125, 11253-11258 reported that n-valeraldehyde was used as a raw material, through cyclization, reduction, and finally through asymmetric reduction to obtain the above-mentioned butyrol Ester derivatives, where expensive chiral catalysts and ligands are used and it is difficult to maintain very high chiral purity

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