Dicyclohexylcarbodiimide → HCID 178454159, compound

Participants

Reaction Conditions

Reaction Steps

N-Methyl-L-histidine methyl ester (1.05 g.) from step a was dissolved in dichloromethane and at 0° C., 1.25 ml of triethylamine was added, followed by N-t-butyloxycarbonyl-L-phenylalanine (1.14 g.), 1-hydroxybenzotriazole hydrate (1.04 g.) and dicyclohexylcarbodiimide (0.89 g.) the mixture was stirred at 0° C. and allowed to slowly warm to 20° C. over a 4-5 hour period. It was then stirred an additional 10 hours. The slurry was filtered, concentrated, redissolved in 100 ml of ethyl acetate, the additional precipitate was filtered, and the filtrate was washed with 1N sodium hydroxide (2×10 ml) dried over magnesium sulfate, and concentrated to give 0.84 g. of an off-white solid. Recrystallization of this material from ethyl acetate gave 0.47 g. of the title compound as a colorless powder. Additional material was obtained as follows. The combined filtered drying agent and second (from ethyl acetate) precipitate above were heated in methanol, and the resultant suspension was cooled, filtered and the filtrate was concentrated to give a solid which was chromatographed on silica in ethanol-dichloromethane to give 0.857 g. of the pure title substance. 1H NMR, CDCl3, 250 mHz, partial, 1.39 (s, 9H, Boc), 2.80 (S, 3H, N-CH3 ), 2.90 and 3.03 (m), 3.35 (m, 1H), 3.70 (s, 3H, OCH3), 4.75 (dt, 1H), 5.15 (dt, 1H), 5.3 (d, BOCNH), 6.84 and 7.68 (1H ea, imidazolyl CH), 7.1-7.4 (m, aromatic). Singlets at 7.55 and 6.74 suggested about 10% of the substance exists in another rotameric form (imidazolyl CH resonances).

Provenance & Evidence