合成路线1

Synthesis of intermediate (I): 1a) Dimethyl acetonedicarboxylate (IV) is treated with MgCl2 and triethylamine, giving the corresponding magnesium complex (V), which by cyclocondensation with chloroacetyl chloride and thiourea yields methyl 2-(2-aminothiazol-4-yl)-3-hydroxy-4-(methoxycarbonyl)-2-butenoate (VI). The reduction of (VI) with NaBH4 affords dimethyl 2-(2-aminothiazol-4-yl)-3-hydroxyglutarate (VII), which by successive treatments with benzyloxycarbonyl chloride (to protect the amino group), and with mesyl chloride - triethylamine (to dehydrate the OH group) is converted to methyl 2-[2 (benzyloxycarbonylamino)thiazol-4-y]-4-(methoxycarbonyl)-2-butenoate (VIII). The hydrolysis of (VIII) with aqueous NaOH in toluene gives the corresponding diacid (IX), which is selectively esterified with benzyl alcohol in acidic medium yielding (I). 1b) The reaction of methyl 2-(2-aminothiazol-4-yl)acetate (X) with beozyloxycarbonyl chloride and NaHCO3 gives the protected compound (XI), which is condensed with methyl 3-methoxyacrylate (XII) by means of sodium methoxide in DMF to yield dimethyl ester (VIII), already obtained.