Synthesis Of Trimebutine Maleate

Trimebutine Maleate is a new class of gastrointestinal dynamic adjustment medicine widely used for irritable bowel syndrome and intestinal diseases.Linical trials indicate that Trimebutine Maleate has reliable efficacy and less adversreations.By referring to relate literatues and patents,two methods was abtained sta rting from the DL-phenylglycine.The two routes were as following:Routes we re accomplished in eight steps following the aequnece of the protection of carb oxyl group,amino protection,alkylation,de-protection of the amino group,met hylation,reduction of ester,alcoholysis of acyl chloride,complexation.(1)The synthesis focused on the protection of amino protection and the ef fects on alkylation.When Benzaldehyde was used as a protectant,the alkylatio n is good.(2)Alkylation system under diffent bases,An allyl group was introduced using allylbromide and sodiumamiide with 80.9%.(3)More attention has been paid to the methylation of formaldehyde-for mic acid system,the molar ratio was ethyl 2-amino-2-phenylbutanoate:37%f ormaldehyde:formic acid:1:2.3:4.0.The reaction time was 4h on the temperat ure of 70 ℃ with 86%.The formaldehyde-formic acid system was more sui table for industy.(4)We try to synthesis 2-Dimethylamino-2-phenylbutanol(7)with the differ ent synthesis routes.First Ethyl 2-amino-2-phenylbutanoate(18)was reduced usi ng sodium borohydride and then methylation to 2-Dimethylamino-2-phenylbutan ol(7).More simple craft,moderate reaction condition and relatively higher yield were more suitable for industy.