Methylamine → 1H-Imidazole-4-carboxylic acid, 5-amino-1-methyl-, ethyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of ethyl 3-nitriloalaninate (26.7 g, 208 mmol) and triethyl orthoformate (34.6 mL, 208 mmol) in 340 mL of acetonitrile is heated to 90° C. and stirred for 70 min. After cooling to RT, methylamine (25.9 mL of a 33 wt % solution in EtOH, 208 mmol) is added, followed by 20 h of stirring at RT. The reaction mixture is then concentrated in vacuo and dissolved in approx. 200 mL of 1N HCl. The aqueous solution is washed with CH2Cl2 (3×100 mL), basified to pH=9-10 with solid NaHCO3, and extracted with CH2Cl2 (5×100 mL). The combined CH2Cl2 extracts are dried (Na2SO4), filtered, and concentrated to give a brown solid. The solid is slurried in EtOAc, filtered, and washed with Et2O to give the title compound as an off-white solid. 1H NMR (400 MHz, CDCl3) δ 7.03 (1H, s), 4.88 (2H, bs), 4.33 (2H, q, J 7.2), 3.45 (3H, s), 1.37 (3H, t, J 7.2).

Provenance & Evidence