Ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate

2199-51-1

2199-59-9

The general procedure for the synthesis of ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate from ethyl 2,4-dimethylpyrrole-3-carboxylate was as follows: dimethylformamide (322 g) was mixed with dichloromethane (3700 mL) and cooled to 4 °C in an ice bath, followed by the slow addition of phosphorus trichloride (684 g) under stirring. Solid ethyl 2,4-dimethyl-1H-pyrrole-3-carboxylate (670 g) was added in batches over 15 min and the maximum temperature was controlled at 18 °C during the reaction. The reaction mixture was heated to a reflux state maintained for 1 h. Subsequently, the temperature was raised to 15 °C by cooling to 10 °C and rapid addition of 1.6 L of ice water. 10N hydrochloric acid (1.6L) was added with vigorous stirring and the temperature was raised to 22°C. The reaction was allowed to stand for 30 minutes to allow the two phases to separate. The two phases were allowed to separate by standing for 30 minutes, during which time the maximum temperature reached 40°C. The pH of the aqueous phase was adjusted to 12-13 with 10N potassium hydroxide (3.8L), and the temperature was maintained at 55°C during the adjustment. After adjustment, the mixture was cooled to 10°C and stirred for 1 hour. The product was collected by vacuum filtration and washed four times with water to afford ethyl 5-formyl-2,4-dimethyl-1H-pyrrole-3-carboxylate (778 g, 100% yield) as a yellow solid. The product was analyzed by 1H-NMR (DMSO-d6) and mass spectrometry to confirm the structure: 1H-NMR δ 1.25 (t, 3H, CH3), 2.44,2.48 (2*s, 2*3H, 2*CH3), 4.16 (q, 2H, CH2), 9.59 (s, 1H, CHO), 12.15 (br s, 1H, NH); MS m/z 195 [M+1].