In a 250 ml round bottom flask equipped with a magnetic stir bar, the potassium carbonate (2.06 g, 14.91 mmol) was suspended in clean, dry N,N-dimethylformamide (50.00 ml, 645.74 mmol) and the mixture was stirred together under nitrogen at room temperature as the 2-chloro-5-nitro-4-(4-o-tolyl-piperazin-1-yl)-benzoic acid 1d (2.54 g, 6.76 mmol) was added in one portion. The mixture was stirred until it appeared all the organic solids were in solution and then iodomethane (0.46 ml, 7.39 mmol) was added. The reaction was diluted with 100 ml of water and the product was extracted from the aqueous using ethyl acetate (3×100 ml). The layers were separated and the organic phases were combined, washed with brine (1×150 ml) and saturated aqueous lithium chloride solution (2×150 ml). The solution was then dried over Na2SO4; the solution was decanted and the solvent was removed under reduced pressure. The compound was purified using silica gel column chromatography, eluting a gradient of 100% heptanes to 75% ethyl acetate in heptane. 2-Chloro-5-nitro-4-(4-o-tolyl-piperazin-1-yl)-benzoic acid methyl ester 10a (2.45 g, 6.27 mmol) was isolated as a yellowish-white solid and was carried on without further purification. LCMS (m/e)=390 (M+H).
