4 - Methoxycarbonyl Fentanyl Synthesis Of Research

Since 20th century 60, 70's, and the modern terrorism has formed, terrorism gradually attracts international news service office's attention, in particular 9.11 events occurrences symbolized the terrorism and the anti-terrorism entering a recent development phase. In 2002, the Russian big theater hostage event, as a result of each kind of reason, finally caused 118 hostages to get killed. When Russia rescued the hostage, useing the powerful analgesic incapacity compound of the fentanyl derivatives. Mainly because the fentanyl derivatives has the special pharmacological action: 1, In rescuing the hostage in the surprise attack event, both may protect the hostage to exempt the massive death, and may be the condition which the kidnapper is in cannot revolt immediately. 2, the fentanyl and its the derivative have the special effect the disintoxicating effect, For instance noloxone and so on μ acceptor to oppress anti- medicinal preparation.As early as Belgian Janssen and so on for the first time has reported the fentanyl of new powerful effect analgesic medicine in the 20th century the beginning of 60's. Hereafter arouseing the enormous interest to the kind of medicine research. Some 4-substitution the fentanyl derivatives, for example 4-methoxycarbonyl fentanyl and 4-methoxymethyl fentanyl are one of strongest types of analgesia activity, among which 4-methoxycarbonyl fentanyl analgesia activity for morphine 10,031 times. Sufentanil and alfentanil develops which from this kind of derivatives have applied to the clinical stability analgesia and the anaesthesia technique; Because it is smaller to the cardiovascular system influence, looked straight ahead in the surgery in the heart to obtain the widespread application.In the present paper, 4-methoxycarbonyl fentanyl was synthesized on the basis of literature, via addition , hydrolysis, esterification, acylation. In the reaction process, the first step was synthesized according to literature; The second step which 85% H₂SO₄ was applied to in was synthesized; The third step was hydrolyzed in the use of cono HCl; The crude was directly used in the next step; The fifth step reaction, firstly propionic acid anhydride was used, but the yield was lower. Then propionyl chloride was used, the final 4-methoxycarbonyl fentanyl was obtained. In the experiment process, the price of key raw material is rather high. Therefore 1-phenethyl-4-piperidone was synthesized, in the use of phenylethylamine and methyl acrylate, via addition, kondensation and decarboxylation. Then 1-phenethyl-4-piperidone was exosyndromed in the use of mp, IR, HNMR ect.Moreover, orthogonal experiment was applied and the microwave catalysis method was used to make the improvement to the partial reaction step, enhanced the production rate, reduced the reaction time and obtained the best response condition.But there was more the by-product.Tn order to study structure-function relationship of 4-methoxycarbonyl fentanyl, and synthesize the powerful activity compound. Gaussian 03 was used and obtain E_homo, E_lumo and charge density of N in the 18 compound.