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

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Reaction Steps

A mixture of 4-fluoro-N2-phenylbenzene-1,2-diamine (1.19 g, 5.88 mmol), (S)-2-tertbutoxycarbonylaminopropionic acid (1.22 g, 6.47 mmol), HOAt (881 mg, 6.47 mmol), 4-methylmorpholine (1.42 mL, 12.95 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.24 g, 6.47 mmol) in DCM (30 mL) was stirred at RT for 21 h. The reaction mixture was then partitioned between additional DCM and an aqueous solution of NaHCO3. The organic layer was dried and concentrated in vacuo and the resulting residue (2.40 g) was dissolved in AcOH (50 mL) and stirred for 48 h at 60° C. After cooling to RT, volatiles were evaporated under reduced pressure and the residue was partitioned between EtOAc and a saturated 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 DCM) affording [(S)-1-(6-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tertbutyl ester as a yellow foam (1.20 g, 57%). LCMS: RT 3.50 min [M+H]+ 356.2

Provenance & Evidence