The oxidation of 3-methoxy-4-methylnitrobenzene (I) with CrO3, H2SO4 and AC2O in acetic acid gives the gem-diacetate (II), which is hydrolyzed with HCl in refluxing dioxane to yield 2-methoxy-4-nitrobenzaldehyde (III). Cyclization of (III) with tosylmethyl isocyanide and K2CO3 in refluxing methanol affords 3-methoxy-4-(5-oxazolyl)nitrobenzene (IV), which is reduced with H2 over Pd/C in ethyl acetate to provide the corresponding aniline (V). The activation of (V) with carbonyldiimidazole (CDI) in THF gives the carboxamide (VI), which is condensed with 3-(tert-butoxycarbonylaminomethyl)aniline (VII), obtained by reaction of 3-aminobenzylamine with Boc2O, and DMAP in refluxing THF to yield the urea (IX). Deprotection of (IX) with TFA in dichloromethane affords the free benzylamine (X), which is finally condensed with the 3-furyl ester of the succinimidyl-activated carbonate (XI) by means of TEA in dichloromethane/DMF.
The desired intermediate 5-(2-methoxy-4-nitrophenyl)oxazole (IV) has been obtained as follows. The carbonylation of 2-methoxy-4-nitrophenyldiazonium tetrafluoroborate (I) by means of carbon monoxide catalyzed by Pd(OAc)2 and Tes-H in ethyl ether/acetonitrile gives 2-methoxy-4-nitrobenzaldehyde (II), which is cyclized with tosylmethyl isocyanate (III) by means of K2CO3 in refluxing methanol to afford the target intermediate 5-(2-methoxy-4-nitrophenyl)oxazole (IV) (see scheme no. 24362801a, intermediate (IV)).