Preparation method of (R)-3-propyl-gamma-butyrolactone

Abstract

The invention discloses a preparation method of (R)-3-propyl-gamma-butyrolactone. The method comprises the following steps: with (S)-3-hydroxyl-gamma-butyrolactone as an initial raw material, activating hydroxyl by using sulfonate, reacting the hydroxyl-activated compound with a Grignard reagent in the presence of a copper catalyst, a cocatalyst and a nitrogen-containing compound to generate (R)-3-propyl-gamma-butyrolactone. The preparation method has the advantages that the process route is simple, the raw materials are cheap and easy to obtain, the synthesis route is short, the reaction conditions are mild, the operation is simple and convenient, the yield is high, and the stereoselectivity is good, the problems of the prior art that chiral separation and chiral column separation are needed in reaction, the yield is low and the chemical selectivity is poor are solved, and an important value is provided for the process research of brivaracetam.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical chemical synthesis, and in particular relates to a preparation method of an antiepileptic drug buvaracetam intermediate (R)-3-propyl-γ-butyrolactone. Background technique

[0002] Brivaracetam is the third-generation antiepileptic drug developed by UCB in Belgium. It was approved by EMEA and FDA in January and February 2016, respectively, for the treatment of epilepsy in adults and adolescents over 16 years old. Adjunctive treatment of partial seizures, with or without secondary generalized seizures. Brivaracetam is a structural derivative of levetiracetam, which is a highly selective and high-affinity synaptic vesicle protein 2A ligand. ) combine to affect synaptic function, and at the same time as a high-affinity sodium channel inhibitor, significantly improve antiepileptic activity. Ibuvaracetam has better safety and pharmacokinetic properties, especially the good tolerance of the central nervou...

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