Synthesis
To a stirred solution of 1-(4-bromo-1-methyl-1H-pyrrol-2-yl)-2,2,2-trichloroacetophenone (3.28 g, 10.74 mmol, 1 eq.) in anhydrous MeOH (30 mL) was slowly added sodium methanol solution (0.5 mL) using a syringe. Sodium methanol solution was prepared from 60% NaH in mineral oil (43 mg, 1.07 mmol, 0.1 equiv) and was pre-washed with hexane. The reaction mixture was heated to reflux for 30 min until TLC analysis showed complete consumption of the feedstock. Subsequently, a few drops of concentrated H2SO4 were added to the reaction solution to neutralize the base (pH 2). Excess MeOH was removed by vacuum evaporation and the resulting oil was redissolved in EtOAc (50 mL) and washed with deionized water (40 mL). The aqueous layer was back-extracted with EtOAc (3 x 40 mL), and the organic phases were combined, dried with anhydrous MgSO4, filtered and concentrated in vacuum to afford methyl 4-bromo-1-methyl-1H-pyrrole-2-carboxylate as a light white solid (2.28 g, 97% yield). The product was confirmed by IR, 1H-NMR, 13C-NMR and EIMS characterization.
References
[1] Patent: WO2013/164592, 2013, A1. Location in patent: Page/Page column 50
[2] Patent: WO2013/164593, 2013, A1. Location in patent: Page/Page column 42
[3] Journal of Organic Chemistry, 2004, vol. 69, # 23, p. 8151 - 8153
[4] Tetrahedron Letters, 1996, vol. 37, # 43, p. 7801 - 7804
[5] European Journal of Medicinal Chemistry, 2016, vol. 117, p. 47 - 58
