4-Methylmorpholine → (S)-tert-butyl 1-(6-fluoro-1-phenyl-1H-benzo[d]imidazol-2-yl)propylcarbamate

Participants

Reaction Steps

A mixture of 4-fluoro-N2-phenylbenzene-1,2-diamine (199 mg, 0.98 mmol), (S)-2-tertbutoxycarbonylaminobutyric acid (219 mg, 1.08 mmol), HOAt (147 mg, 1.08 mmol), 4-methylmorpholine (0.238 mL, 2.16 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (207 mg, 1.08 mmol) in DCM (5 mL) was stirred at RT for 2 h. The reaction mixture was partitioned between DCM (50 mL) and a saturated solution of NaHCO3. The organic layer was dried (Na2SO4), concentrated in vacuo and the resulting residue dissolved in AcOH (10 mL) and stirred for 18 h at 70° C. After cooling to RT, the volatiles were evaporated under reduced pressure and the residue was partitioned between DCM (50 mL) and a saturated aqueous solution of NaHCO3. The organic layer was washed with brine, dried (Na2SO4) and then concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) to afford the title compound as a beige solid (234 mg, 64%). LCMS (Method C): RT 3.82 min [M+H]+ 370.5.

Provenance & Evidence