Hydrochloric Acid → HCID 18687952, compound

Participants

Reaction Steps

4-Aminobenzoic acid (5.0 g, 36.46 mmol) was dissolved in a mixed solvent of 1,4-dioxane/1N sodium hydroxide (1/1, 50 ml), and a 1,4-dioxane solution (9.5 g, 43.75 mmol/25 ml) of di-t-butyl carbonate was added dropwise to the solution under cooling with ice water. The mixture was stirred at room temperature. After 7.5 hours, additional di-t-butyl carbonate (1.5 g) was added to continue stirring. After 24 hours, 6N hydrochloric acid was added to the reaction mixture to acidify it, and the solvent was then distilled off under reduced pressure. The resultant residue was dissolved in ethyl acetate, and the solution was washed 4 times with water and once with saturated brine and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure to obtain 9.28 g (39.10 mmol) of 4-butoxycarbonylaminobenzoic acid as a crude product. This compound was dissolved together with benzyl alcohol (4.23 g, 39.10 mmol) and N,N-dimethylaminopyridine (478 mg, 3.91 mmol) in N,N-dimethylformamide (100 ml), and 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (8.99 g, 46.92 mmol) was added to the solution under cooling with ice water. The mixture was stirred at room temperature for 8 hours. The reaction mixture was diluted with ethyl acetate, washed with water (twice), a 10% aqueous solution of citric acid, a saturated aqueous solution of sodium hydrogencarbonate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was distilled off under reduced pressure, and the residue was subjected to column chromatography on silica gel (toluene:ethyl acetate=20:1) to obtain 4.09 g (12.5 mmol) of a benzyl ester. The thus-obtained ester was dissolved in ethyl acetate (70 ml), and 4N hydrochloric acid/ethyl acetate (70 ml) was added to the solution. The mixture was stirred at room temperature. After 1.5 hours, additional 4N hydrochloric acid/ethyl acetate (70 ml) was added to continue stirring. After 1 hour, the reaction was stopped, and solids deposited were collected by filtration. The thus-obtained solids were suspended in ethyl acetate, and the suspension was ultrasonically washed and then filtered to obtain 2.86 g of the title compound.

Provenance & Evidence