Synthesis
General procedure for the synthesis of 3-methyl-1H-pyrrole-2-carboxylic acid from methyl 3-methyl-1H-pyrrole-2-carboxylate:
1. dissolve methyl 3-methyl-1H-pyrrole-2-carboxylate (2.0 g, 14.37 mmol, purchased from Otava Chemicals, Catalog No. 1056278) in 50 mL of methanol.
2. 21.5 mL of 2N aqueous sodium hydroxide was added to the solution.
3. The reaction mixture was stirred overnight at room temperature, then warmed to 60 °C and continued stirring for 20 hours.
4. Upon completion of the reaction, the methanol was removed by vacuum evaporation.
5. The remaining aqueous solution was neutralized with 21.5 mL of 2N hydrochloric acid solution.
6. The product was extracted using a 95:5 chloroform/methanol mixture.
7. The organic phase was washed with brine, dried over magnesium sulfate, filtered and evaporated in vacuum.
8. 1.38 g (77% yield) of the target compound 3-methyl-1H-pyrrole-2-carboxylic acid was obtained as a brown solid.
LRMS (m/z): 126 (M + 1)+.
1H NMR (400 MHz, DMSO) δ 12.06 (s, 1H), 11.30 (s, 1H), 6.84-6.75 (m, 1H), 6.02-5.93 (m, 1H), 2.24 (s, 3H).
References
[1] Patent: WO2012/146666, 2012, A1. Location in patent: Page/Page column 105
[2] Patent: EP2518070, 2012, A1. Location in patent: Page/Page column 44
[3] Patent: WO2014/60431, 2014, A1. Location in patent: Page/Page column 91
[4] Patent: WO2014/60432, 2014, A1. Location in patent: Page/Page column 122; 123
