合成路线1

Jones oxidation of 2-fluoro-4-nitrotoluene (I) afforded carboxylic acid (II). After activation of (II) as the corresponding acid chloride with SOCl2, reaction with lithium tert-butoxide furnished the tert-butyl ester (III). Reduction of the nitro group of (III) by means of iron powder in the presence of ammonium chloride gave amine (IV), which was converted to carbamate (V) upon treatment with benzyl chloroformate. The chiral oxazolidinone (VII) was prepared by condensation of the lithium salt of carbamate (V) with (R)-glycidyl butyrate (VI). After activation of the primary hydroxyl of (VII) as the corresponding mesylate, displacement with NaN3 in hot DMF provided the alkyl azide (VIII). Tert-Butyl ester cleavage in (VIII) by means of trifluoroacetic acid afforded the carboxylic acid (IX). Curtius rearrangement of acid (IX) with diphenylphosphoryl azide in the presence of tert-butanol generated the tert-butyl carbamate (X). Further N-alkylation of carbamate (X) using iodomethane and LiH gave the N-methyl analogue (XI). Then, reduction of the azido group of (XI) to the primary amine (XII) was accomplished by treatment with triphenylphosphine followed by aqueous hydrolysis.