反应详情

温度

0 °C

To a solution of sodium nitrite (714 g, 10.2 mol) in 700 ml of water at 50° C.±5° C. was added over a period of 3 hours a solution of mucobromic acid (48) (700 g, 2.7 mol) in 700 ml of warm ethanol. The reaction was stirred for 15 minutes, cooled to 0° C., and 700 ml of ethanol was added. The resulting orange precipitate was collected by vacuum filtration and dried in vacuo to yield sodium nitromalondialdehyde monohydrate (305 g, 1.9 mol) which was used in the next step without further purification. Glycine ethyl ester (300 g, 2.9 mol) and nitromalondialdehyde monohydrate (305 g, 1.9 mol) were placed in a 12 l round bottom flask and slurried with a mechanical stirrer in 560 ml of methanol and 280 ml of water. Sodium hydroxide (800 g, 20 mol) dissolved in 1.6 l water was added to the solution at a rate which maintained the temperature at 50° C. The reaction was cooled to 0° C. with an ice bath and neutralized to pH 0 with 1.7 1 HCl (conc.) while maintaining the temperature below 10° C. A black precipitate was removed by filtration through Celite and the product was extracted with 20 liters of ethyl acetate. The organic layer was dried with sodium sulfate and concentrated in vacuo to provide 4-nitropyrrole-2-carboxylic acid (140 g, 0.9 mol) as a brown solid which was used without further purification. To a solution of 4-nitropyrrole-2-carboxylic acid (140 g, 0.9 mol) dissolved in 180 ml of methanol was added 8 ml of concentrated sulfuric acid. The solution was refluxed for 15 hours, cooled to 0° C. and 90 ml of water was added. The solution was then allowed to stand at -20° C. for 2 days. The resulting light brown crystals were collected by vacuum filtration to yield pure methyl 4-nitropyrrole-2-carboxylate (49) (105 g, 0.62 mol) in 23% overall yield. 1H NMR (DMSO-d6) δ 14.2 (br s, 1H), 7.74 (d, 1H, J=1.6 Hz), 7.35 (d, 1H, J=1.7 Hz), 3.73 (s, 3H).

1. filtrationThe resulting orange precipitate was collected by vacuum filtration
2. customdried in vacuo