Synthesis
Step 2: Synthesis of ethyl 3-amino-1H-pyrrole-2-carboxylate
A solution of diethyl 2-((2-cyanoethenyl)amino)malonate (30 g, 119.3 mmol, 1.00 equiv, 90% purity) in ethanol (420 mL) was added to a 1000 mL round bottom flask. Sodium ethoxide (80 mL, 21% w/w ethanol solution) was subsequently added. The reaction mixture was stirred at room temperature for 3 days. Upon completion of the reaction, the reaction was quenched by the addition of acetic acid (15 mL) and the mixture was subsequently concentrated under reduced pressure to remove the solvent. The concentrated residue was dissolved in dichloromethane (200 mL) and washed sequentially with saturated aqueous sodium bicarbonate (2 × 100 mL) and brine (1 × 100 mL). The organic layer was dried with anhydrous sodium sulfate, filtered and concentrated. The residue was dried under high vacuum (HV) to give ethyl 3-amino-1H-pyrrole-2-carboxylate (10 g, 49% yield) as an orange slurry.
References
[1] Tetrahedron, 2014, vol. 70, # 31, p. 4631 - 4639
[2] Patent: US2012/202785, 2012, A1. Location in patent: Page/Page column 128-129
[3] Journal of Organic Chemistry, 1999, vol. 64, # 22, p. 8411 - 8412
[4] Chemical Biology and Drug Design, 2011, vol. 78, # 6, p. 932 - 940
