Synthesis And Characterization Of 4-Dimethylaminocrotonic Acid As Medicine Intermediate

4-Dimethylaminocrotonic acid was synthesized successfully through three step in this paper, which is one kind of useful intermediate of anti-cancer drugs. For the first step, trimethylsilyl crotonate was synthesized using crotonic acid and trimethylchlorosilane. The second step was to synthesize trimethylsilyl-4- bromocrotonate via bromine substitution reaction using trimethylsilyl crotonate and N-bromobutanimide. The last step was the synthesis of the target produst,4-dimethylaminocrotonic acid using trimethylsilyl-4-bromocrotonate and dimethy-lamine in the solution of tetrahydrofuran.The structures of the products were chatacterised and the purity was determined by the use of gas chromatograph-mass spectrometer(GC-MS), NMR spectrometer, melting point mensuration and so on. The reaction conditions were optimized by the Single-factor experimentation and Orthogonal experimentation.Under optimized conditions (the reactant mole ratio of n(crotonic acid):n(trimethylchlorosilane)=1.0:1.2 reacted at 20℃for 10h), the yield of the trimethylsilyl crotonate was 84.1% with 96.4% purity.Then reaction of trimethylsilyl crotonate with 1.2 equiv. N-bromobutanimide at 77℃for five hours gave trimethylsilyl-4-bromocrotonate in the yield of 71.2% with 87.3% purity.After optimization,4-dimethylaminocrotonic acid was finally obtained in the yield of 73.5% with 97.1% purity from reaction of trimethylsilyl-4-bromocrotonate and 2.0 equiv. dimethylamine at 20℃for 30 minutes.