In a 10 ml round bottom flask equipped with a magnetic stir bar and a nitrogen inlet, the 2-chloro-5-nitro-4-(4-o-tolyl-piperazin-1-yl)-benzoic acid methyl ester 10a (115.70 mg, 0.30 mmol) was combined dry with the tricyclohexylphosphine (20.00 mg, 0.07 mmol) and was then taken up in clean, dry 1,4-dioxane (0.75 ml, 8.77 mmol) and the mixture was stirred at room temperature under nitrogen atmosphere until all solids were in solution. While that was stirring, the potassium phosphate tribasic (126.00 mg, 0.59 mmol) was dissolved in water (0.50 ml, 27.75 mmol) and once complete dissolution was achieved, the basic solution was added to the stirring dioxane solution. The reaction mixture was then placed under vacuum for 10 min and was then flushed with nitrogen. The 2-((E)-2-ethoxy-vinyl)-4,4,5,5-tetramethyl-[1,3,2]dioxaborolane (64.60 mg, 0.33 mmol) was added to the solution, and the system was degassed once more. After flushing the system with nitrogen once more, the tris(dibenzylideneacetone)dipalladium (27.00 mg, 0.03 mmol) was added in one portion and the flask was fitted with a jacketed reflux condenser and the system was purged under vacuum once more. The reaction mixture system was then flushed with nitrogen and warmed to 100° C. The reaction was allowed to stir overnight under nitrogen at elevated temperatures. The reaction was cooled to room temperature and the mixture was filtered through Celite, washing heavily with ethyl acetate. The liquid filtrate was then collected and the solvent was removed under reduced pressure, absorbing the residue onto Celite. The product was then purified using silica gel column chromatography, eluting a gradient of 100% heptanes to 75% ethyl acetate in heptane. The product 2-((E)-2-ethoxy-vinyl)-5-nitro-4-(4-o-tolyl-piperazin-1-yl)-benzoic acid methyl ester 10b (97.10 mg, 0.23 mmol), was isolated as an off-white, slightly yellowish solid. LCMS (m/e)=426 (M+H).
