synthesis of (±)-baclofen using wittig olefination–claisen rearrangement

Baclofen, a lipophilic derivative of gaba (gamma-aminobutyric acid), which acts as an inhibitory neurotransmitter in cns (central nervous system) was synthesized by witting olefination-claisen rearrangement protocol. 4-chlorobenzaldehyde was subjected to wittig reaction with ((allyloxy)methylene)triphenyl-phosphane to give 1-(2-(allyloxy)vinyl)-4-chlorobenzene which on heating under reflux condition in toluene underwent claisen rearrangement to give 2-(4-chlorophenyl)pent-4-enal. aldehyde was reduced to corresponding alcohol 2-(4-chlorophenyl)pent-4-en-1-ol as an important precursor which can be used for the synthesis of baclofen and different gaba derivatives. further tosylation, formation-reduction of azide group and oxidative ozonolysis of terminal double bond yields 4-amino-3-(4-chlorophenyl)butanoic acid in excellent yield. therefore, an efficient method was developed for the synthesis of (±)-baclofen in a simple seven step procedure.