Trifluoroacetic acid → 4-((1r)-1-{n-Methyl-n-[(1r)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-(2-naphthyl)ethyl]carbamoyl}-2-(2-naphthyl)ethyl)carbamoylpiperidine-1-carboxylic acid tert-butylester

Participants

Reaction Steps

N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.42 g, 2.2 mmol) and 1-hydroxybenzotriazole monohydrate (0.34 g, 2.2 mmol) were added to a solution of N-tert-butoxycarbonyl-4-piperidine carboxylic acid (0.50 g, 2.2 mmol) in N,N-dimethylformamide (5 ml). After 30 min at 20° C. a mixture of (2R)-2-amino-N-methyl-N-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-(2-naphthyl)ethyl]-3-(2-naphthyl)propionamide, trifluoroacetic acid (0.9 g, 1.54 mmol) and triethylamine (0.16 g, 1.54 mmol) in N,N-dimethylformamide (10 ml) were added. After 18 h at 20° C. the reaction mixture was poured on water (85 ml) and extracted several times with ethyl acetate (total 90 ml). The organic phases were collected and washed with aqueous citric acid (10%, 15 ml), a saturated solution of sodium hydrogencarbonate (15 ml) and water (3×15 ml). After drying (magnesium sulfate) the solution was concentrated in vacuo and the residue was chromatographed on silica (110 g) using ethyl acetate and heptane (1:1) as eluent to give 0.50 g of 4-((1R)-1-{N-methyl-N-[(1R)-1-(3-methyl-[1,2,4]oxadiazol-5-yl)-2-(2-naphthyl)ethyl]carbamoyl}-2-(2naphthyl)ethyl)carbamoylpiperidine-1-carboxylic acid tert-butylester.

Provenance & Evidence