Uses
ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate is used in the preparation of blue pyrrole dyes. It is also used as an intermediate in the synt hesis of receptor tyrosine kinase (RTK) inhibitors and their metabolites.
Synthesis
Step (ii): Preparation of 2,4-dimethyl-1H-pyrrole-3-carboxylic acid ethyl ester
In a 10-liter four-necked round-bottomed flask equipped with a mechanical stirrer, thermometer casing, gas introduction tube, and air condenser, 3,5-dimethyl-1H-pyrrole-2,4-dicarboxylic acid 2-tert-butyl ester 4-ethyl ester (II) (1.5 kg, 5.6 mol) and isopropanol (4.5 L) were added and stirred at 25-30 °C. Concentrated hydrochloric acid (2.2 L) was added slowly through the addition funnel. After addition, the reaction mixture was warmed up to 45-50 °C and maintained at this temperature until complete cessation of gas release. The reaction progress was monitored by thin layer chromatography (TLC). Upon completion of the reaction, the solution was cooled to 25-30 °C and quenched in an ice-water bath. The product was separated by filtration and dried at 50 °C. A dried product of 721.3 g was obtained with 77.3% yield and >96% HPLC purity.
References
[1] Synlett, 2010, # 17, p. 2561 - 2564
[2] Bioorganic and Medicinal Chemistry Letters, 2011, vol. 21, # 10, p. 3062 - 3065
[3] Journal of the American Chemical Society,
[4] Journal of the American Chemical Society, 2009, vol. 131, p. 8578 - 8586
[5] Journal of Medicinal Chemistry, 2010, vol. 53, # 1, p. 139 - 146
