Triethylamine → HCID 178472439, compound

Participants

Reaction Steps

3-{1-[(cis-4-Ethoxycarbonylcyclohexyl)carbamoyl]cyclopentyl}-2-[3-(benzyloxycarbonyl)phenylmethyl]propanoic acid tert-butyl ester (370 mg, 0.60 mmole) was dissolved in tetrahydrofuran (30 ml) and was stirred with 5% palladium on carbon catalyst (50 mg) under an atmosphere of hydrogen at 50 p.s.i. (3.45 bar) for 5 hours. Further catalyst (50 mg) was added and the hydrogenation was continued for 48 hours. The catalyst was removed by filtration and the solvent evaporated to give a yellow oil. Chromatography on silica gel eluting with a mixture of methanol and ethyl acetate (1:4 to 1:1 by volume) gave a colourless oil. The oil (240 mg) was added to a solution of 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (170 mg, 0.91 mmole), 1-hydroxybenzotriazole (140 mg, 0.91 mmole), triethylamine (182 mg, 1.80 mmole) and methylamine hydrochloride (31 mg, 0.45 mmole) in dry methylene chloride (20 ml), and the mixture was stirred at room temperature for 6 days. The solvent was evaporated under reduced pressure and the residue partitioned between ethyl acetate and water. The aqueous layer was acidified with 2N hydrochloric acid, separated and extracted three times with ethyl acetate. The organic fractions were combined and washed sequentially with saturated aqueous sodium bicarbonate solution, water and brine. Drying (MgSO4) and evaporation under reduced pressure gave a yellow oil which was chromatographed on silica gel eluting with a mixture of ethyl acetate and pentane (1:1 by volume). Azeotroping with methylene chloride gave the desired amide as a colourless oil (200 mg, 80%). Found: C,67.58; H,8.80; N,5.22. C31H46N2O6.1/8 CH2Cl2 requires: C,67.57; H,8.42; N,5.06%.

Provenance & Evidence