Sodium Bicarbonate → [3-((R)-1-{5-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-3-fluoro-pyridin-2-yl}-ethylcarbamoyl)-oxetan-3-yl]-carbamic acid 9H-fluoren-9-ylmethyl ester

Participants

Reaction Steps

To a solution of 3-(9H-fluoren-9-ylmethoxycarbonylamino)-oxetane-3-carboxylic acid (77.4 mg, 0.228 mmol, intermediate 8) in dry DMF (2 ml) were added N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (48.1 mg, 0.251 mmol) and 1-hydroxybenzotriazole hydrate (38.4 mg, 0.251 mmol) at room temperature. The resulting colorless solution was stirred for 5 min before a solution of (R)-1-{5-[5-chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-3-fluoro-pyridin-2-yl}-ethylamine (80.0 mg, 0.228 mmol, step B) in dry DMF (2 ml) was added. This mixture was stirred at room temperature for 1.5 h. Then water was added, the pH was adjusted to 7 with sat. NaHCO3 solution and the mixture was extracted three times with EtOAc. The combined organic layers were washed three times with water and then with brine, dried with Na2SO4 and evaporated. The remaining light brown foam was purified by chromatography (silica gel; DCM/MeOH 98:2-95:5) and the title compound was obtained as off white foam (150 mg, 98%). MS: 672.3 [M+H]+.

Provenance & Evidence