(2S)-2-amino-6-(((tert-butoxy)carbonyl)amino)hexanoic acid → HCID 70092905, compound

Participants

Reaction Steps

N,N'-disuccininyl carbonate (5.12 g), 2.44 g of phenethyl alcohol and 0.49 g of 4-dimethylaminopyridine were stirred in methylene choride for 3 days. The reaction mixture was washed with water, dried over anhydrous sodium sulfate and concentrated to dryness under reduced pressure. The residue was crystallized from ether. The crystals were collected by filtration to give 3.5 g of N-(phenethyloxycarbonyloxy)succinimide (mp. 69°-72° C.). N6 -t-butoxycarbonyl-L-lysine (2.53 g) was dissolved in a mixture of 30 ml of acetonitrile and 50 ml of 5% potassium carbonate, and 2.9 g of N-(phenethyloxycarbonyloxy)succinimide was added. The mixture was stirred at room temperature for 1 hour. The reaction mixture was washed with chloroform. The aqueous layer was acidified with 10% citric acid, and extracted with chloroform. The extract was dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure to give 4.5 g of N6 -t-butoxycarbonyl-N2 -phenethyloxycarbonyl-L-lysine as an oily substance. An aliquot (1.26 g) of the oily substance and N,N'-disuccinimidyl carbonate were stirred in ethyl acetate for 3 hours, and then an ethyl acetate solution containing 1.0 g of (2S,3aS,7aS)-1-(gamma-D-glutamyl)octahydro-1H-indole-2-carboxylic acid and 0.256 g of pyridine was added, and the mixture was further stirred for 5 hours. The reaction mixture was extracted with 5% sodium bicarbonate solution. The extract was acidified with 10% citric acid, and extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and concentrated to dryness under reduced pressure. The residue was dissolved in 20 ml of trifluoroacetic acid, left to stand at room temperature for 20 minutes, and thereafter concentrated to dryness under reduced pressure. The residue was subjected to CHP20P column chromatography (0%→60% acetonitrile/water gradient). Fractions containing the desired product were concentrated to dryness under reduced pressure. The residue dissolved in dioxane/water, and lyophilized to give 0.3 g of the captioned compound.

Provenance & Evidence