Synthesis of (±)-Baclofen using Wittig Olefination–Claisen Rearrangement
نویسندگان
1 Department of Chemistry, Savitribai Phule Pune University, Pune, Maharashtra, India
2 Department of Chemistry, Shri Vyankatesh Arts, Commerce and Science College, Deulgaon Raja, Dist. Buldana, Maharashtra, India
3 Department of Chemistry, Savitribai Phule Pune University, Pune, Maharashtra, India
4 Department of Chemistry, Avvaiyar Goverenment College for Women, Karaikal, Puducherry, India
doi
10.22034/jaoc.2021.284219.1018چکیده
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.
