Triethylamine → L-Alanyl-L-proline

Participants

Reaction Conditions

Reaction Steps

L-proline methylester hydrochloride (16.58 g, 100 mmole) was dissolved in chloroform (300 ml), and triethylamine (10.12 g, 100 mmole), 1-hydroxybenzotriazole (13.51 g, 100 mmole) and N-benzyloxycarbonyl-L-alanine (22.32 g, 100 mmole) were added thereto under cooling to -15° C. and stirring. To the solution, while keeping the temperature to less than 0° C., a chloroform solution of N,N'-dicyclohexylcarbodiimide (20.63 g, 100 mmole) was added dropwise. After that, the mixture was stirred for 2 hours at 0° C. and then overnight at room temperature. The thus precipitated N,N'-dicyclohexylurea was separated by filtration, and the solution was washed with 10% aqueous sodium bicarbonate, water, 1N hydrochloric acid and water in the order given, and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure and to the residue thus obtained 1N sodium hydroxide (150 ml) was added. The mixture was stirred for 3 hours at 30° C. The thus precipitated N,N'-dicyclohexylurea was separated by filtration, and the filtrate was adjusted to pH 2.5 with 6N hydrochloric acid and was extracted twice with chloroform (200 ml). The chloroform layer was dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The thus obtained residue was dissolved in 50% methanol (300 ml), and-hydrogen gas was passed through the solution in the presence of 2% palladium-carbon as a catalyst for 2 hours at 40° C. The catalyst was separated by filtration and the solvent was distilled off under reduced pressure The residue thus obtained was recrystallized from water and ethanol to give L-alanyl-L-proline (13.41 g; 72.0%).

Provenance & Evidence