Aniline → 4-Phenylaminomethyl-1H-pyrrole-2-carboxylic acid ethyl ester

Participants

Reaction Steps

0.2012 g (1.20 mmol) of 4-formyl-1H-pyrrole-2-carboxylic acid ethyl ester was dissolved in 4.8 mL (0.25 M) of 5% acetic acid in methanol. Aniline (0.13 mL g, 1.44 mmol) was added, and the reaction was stirred at room temperature under nitrogen for 45 minutes, then sodium cyanoborohydride (0.1244 g, 1.98 mmol) was added slowly and the reaction was allowed to stir at room temperature overnight. About 2 mL of saturated K2CO3 were added, and the reaction was extracted twice with ethyl acetate. The combined organics were washed with saturated NaHCO3 (˜3 mL) and brine (˜3 mL), then the combined organics were dried with Na2SO4, filtered and concentrated en vacuo. The crude product was purified by silica gel chromatography (Combiflash column, 85:15 Hexanes:Ethyl acetate) to obtain 0.2663 g (91%) of 4-phenylaminomethyl]-1H-pyrrole-2-carboxylic acid ethyl ester (183) as a colorless viscous oil. Note: Starting material 4-formyl-1H-pyrrole-2-carboxylic acid ethyl ester has an HPLC retention time=7.337 min. 1H (CDCl3, 400 MHz): 89.49 (1H, broad s), 7.19 (2H, dd, J=8.6, 7.3 Hz), 6.73 (1H, tt, J=7.3, 1.1 Hz), 6.66 (2H, dd, J=8.6, 1.1 Hz), 6.91 (1H, d, J=2.0 Hz), 6.90 (1H, d, J=2.0 Hz), 4.33 (2H, q, J=7.2 Hz), 4.19 (2H, s), 3.90 (1H, broad s), 1.36 (3H, t, J=7.2 Hz) ppm. HPLC: 6.936 min.

Provenance & Evidence