Process for the preparation of alpha-substituted-thien-3-ylacetic acid and derivatives thereof.

摘要

A process for the preparation of 3-substituted thiophenes which involves cyclisation of a novel intermediate, avoids the use of previously employed expensive starting materials. The thiophenes are useful for the preparation of penicillins and cephalosporins.

The process is for the preparation of a thiophene of formula (I):
<Chemistry id="chema01" num="0001"><Image id="ia01" he="14" wi="50" file="IMGA0001.TIF" imgContent="chem" imgFormat="TIFF" inline="no" /></Chemistry>where R<Sup>1</Sup> represents a carboxylic acid group, or an ester or amide thereof or a nitrile group; R<Sup>2</Sup> represents a group suitable for use as an α-substituent in the side-chain of a penicillin or cephalosporin; which comprises treating a compound of formula (II):
<Chemistry id="chema02" num="0002"><Image id="ia02" he="23" wi="57" file="IMGA0002.TIF" imgContent="chem" imgFormat="TIFF" inline="no" /></Chemistry>wherein X represents halogen or optionally functionalised hydroxyl, Y represents halogen, hydroxyl, or alkoxy; with a source of nucleophilic sulphur under basic conditions.