Isatoic Anhydride → (2-Aminophenyl)(pyrrolidin-1-yl)methanone

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Reaction Steps

Pyrrolidine (2.46 g, 34.6 mmol) was added dropwise to isatoic anhydride (3.76 g, 23.05 mmol) in tetrahydrofuran (25 mL) at room temperature. The solution was stirred at room temperature for 1.5 hours under a nitrogen atmosphere. The volatiles were removed by evaporation under reduced pressure. The residue was slurried in toluene (50 mL) and the volatiles were removed by evaporation under reduced pressure (2×). The residue was dissolved in hot toluene, then allowed to cool to room temperature. The solution was placed in a freezer for 16 hours to produce a precipitate. The precipitate was filtered and dried to give 3.05 g of crude 1-(2-aminobenzoyl)-pyrrolidine. The crude material (2.65 g) was purified by column chromatography over silica gel using 5-20% ethyl acetate in hexanes. The best fractions were combined and the volatiles were removed by evaporation under reduced pressure. The residue was taken up in dichloromethane (50 mL) and washed with 0.5N sodium hydroxide solution (2×25 mL), washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and the filtrate was concentrated under reduced pressure to yield 1.35 g of 1-(2-aminobenzoyl)pyrrolidine.

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