Triethylamine → 3-Chloro-4'-((R)-1-{[3-(9H-fluoren-9-ylmethoxycarbonylamino)-oxetane-3-carbonyl]-amino}-ethyl)-3'-fluoro-biphenyl-2-carboxylic acid methyl ester

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Reaction Steps

To a solution of 3-(9H-fluoren-9-ylmethoxycarbonylamino)-oxetane-3-carboxylic acid (207 mg, 610 μmol, intermediate 8) in dry DMF (2.11 ml) were added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (129 mg, 671 μmol) and 1-hydroxybenzotriazole hydrate (103 mg, 671 μmol) at room temperature. The colorless solution was stirred for 10 min before a solution of 4′-((R)-1-amino-ethyl)-3-chloro-3′-fluoro-biphenyl-2-carboxylic acid methyl ester hydrochloride (210 mg, 610 μmol) and triethylamine (61.7 mg, 85.0 μl, 610 μmol) in dry DMF (2.11 ml) was added. After addition, the brown solution was stirred at room temperature over night. Then water was added and the pH of the mixture was adjusted to 7 by addition of sat. NaHCO3 solution. The mixture was extracted three times with EtOAc and the combined organic layers were washed with water and brine, dried with Na2SO4 and evaporated. The remaining residue was purified by chromatography (silica gel; DCM/MeOH 99:1-95:5) and the title compound was obtained as white solid (312 mg, 81%). MS: 629.3 [M+H]+.

Provenance & Evidence