Toluene → Ethyl 1-methyl-5-p-toluoylpyrrole-2-acetate

Participants

Reaction Conditions

Reaction Steps

To a stirred and chilled (-60°C.) solution of 5.0 g. (0.022 mole) of ethyl 5-chlorocarbonyl-1-methylpyrrole-2-acetate in 300 ml. of dry toluene is added in one portion 0.70 g. (0.0044 mole) of anhydrous FeCl3, weighed under 5 ml. of toluene and dissolved in 2 ml. of ether. The freshly prepared Grignard solution of 0.023 mole of p-tolylmagnesium bromide in 15 ml. ether is added dropwise, under hydrogen, to the above reaction mixture at such a rate so as to maintain the reaction temperature at -60 ± 2°C. The mixture is stirred at that temperature for another hour, then hydrolyzed with ice water and made strongly acidic with 3N HCl-ice. The aqueous layer is washed 3 times with benzene and the combined organic layers are washed sequentially with 3-dimethylaminopropylamine-ice, 3N HCl-ice, and saturated NaHCO3 solution. The organic layer is dried over anhydrous MgSO4, filtered and the solvent evaporated off to give about 2.0 g. (20%) of a solid residue with thin layer chromatography (film, silica, 1:3 EtOAo/cyclohexane) showing two major spots (rf - 0.54, 0.90). Column chromatography on 50 g. of CC-4 silica and sequential elution with hexane, hexane-benzene, benzene and benzene-ether gives the desired product (eluted with 10% Et2O/benzene) as an oil (0.75 g., 12% yield). Crystallization from MeOH gives about 350 mg. of a white solid, ethyl 1-methyl-5-(p-toluoyl)pyrrole-2-acetate, m.p. 68°-70°C.

Provenance & Evidence