Dimethylformamide → 3-(5-formyl-4-methyl-1H-pyrrol-3-yl)propanoic acid

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Reaction Conditions

Reaction Steps

Dimethylformamide was charged to a 500 mL, 3 neck round bottom flask equipped with mechanical stirring, a thermometer, and a dropping funnel, and maintained under a nitrogen atmosphere. The flask was cooled to 0° C., and 58.4 mL of phosphorus oxychloride was added dropwise over 80 min. Dichloroethane (280 mL) was added, and the mixture was allowed to warm to room temperature, and then was cooled to −10° C. 3-(2-Methoxycarbonylethyl)-4-methylpyrrole (55.7 g) dissolved in 80 mL of dichloroethane was added dropwise over 1 hr, and the mixture stirred for another 35 min. The mixture was rotary evaporated at <30° C. The fluid residue was poured into 2700 mL of ice-cold 2 N sodium hydroxide solution. The resulting solution was heated to 88° C. over 20 minutes and then was maintained at this temperature for an additional 30 minutes. The solution was cooled to ambient temperature and was extracted with 200 mL of ethyl ether. The aqueous solution was cooled to 0° C. and was acidified to pH 3.5 by slowly adding about 1350 mL of 5 N hydrochloric acid. The yellow precipitate was collected by vacuum filtration, was washed four times with 100 mL of water each time, and was dried in a vacuum oven at ambient temperature to give 54.4 g (90.2% yield) of crude 4-(2-carboxyethyl)-2-formyl-3-methylpyrrole.

Provenance & Evidence