Synthesis
50 mL of SOCl2 was slowly added dropwise to a solution of pyrrole-2-carboxylic acid (1) (16.65 g, 0.15 mol) dissolved in 10 mL of MeOH at 0 °C for a controlled time of 30 min. Subsequently, the reaction mixture was warmed up to 35 °C with continuous stirring for 24 hours. Upon completion of the reaction, the solvent was removed by vacuum evaporation, and the resulting residue was purified by column chromatography with the eluent being a mixed solvent of ethyl acetate/petroleum ether, which ultimately afforded Intermediate 2 as a white solid in 85% yield with a melting point of 72-73 °C.
References
[1] Canadian Journal of Chemistry, 2002, vol. 80, # 12, p. 1662 - 1667
[2] Bioorganic and Medicinal Chemistry, 2013, vol. 21, # 22, p. 7091 - 7100
[3] Journal of the Chemical Society - Perkin Transactions 1, 1997, # 20, p. 2997 - 3003
[4] Patent: EP1386913, 2004, A1. Location in patent: Page 88
[5] Patent: EP986382, 2008, B1. Location in patent: Page/Page column 23
