The New Synthetic Process Of Lacosamide

This thesis is based on the synthesis process of lacosamide(1), which is aimed toobtain a more pure final product and improve reaction conditions with one completely newapproach according to the principle of drug synthesis design and documents for thesynthesis of lacosamide.Lacosamide is a new type of anti-seizure drugs, it is mainly for the adjuvant treatmentof diabetic neuropathic pain and adult epilepsy patients, and compared with similar drugsare better tolerated. Therefore, the process research of lacosamide has the very vitalsignificance.Specific synthetic approach can be described as follows:Firstly, using(7) as the starting material, the intermediate (R)-2-amino-3-hydroxyl-prop-ionic acid methyl ester hydrochloride (6) was prepared by esterification. Secondly, usingthe protecting group to obtain (R)-2-tert-butoxycarbonylamino-3-hydroxy-propionic acidmethyl ester(5), and then, the intermediate (R)-2-tert-butoxycarbonylamino-3-hydroxy-N-benzyl-propa-namide (4) reacted with benzylamine, and fourth, using dimeylsulfate toobtain intermediate (R)-2-tert-butoxycarbonylamino-3-methoxy-N-benzylpropanamide (3),and deprotection to give the intermediate (R)-2-amino-3-meth-oxy-N-benzylamide (2);Finally, obtain the final product lacosamide(1) by acetylation. The author has conductedthe six-step reaction process improvements, and has obtained the most appropriate processthrough experiments. The total yield of six steps is65.5%. The physical parameters ofintermediate (6)、(5)、(4)、(3)、(2) and (1) is similar to that of the references, andlacosamide(1) have been confirmed by1H NMR and MS.Optimized synthetic route has the features: Firstly, every step of the reaction is easy toindustrialize and can achieve a higher yield; Secondly, compared with the previousliteratures, we design a new synthesis route of lacosamide.In this paper, based on the synthetic route and reaction conditions of lacosamide,weredrawn up the process diagrams for each step reaction to provide a guarantee for apreliminary design. The design and development of lacosamide can effectively reduce the cost, and hasbroadly application, the larger social and economic value.