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

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

1. customThe reaction mixture was then partitioned between additional DCM
2. customThe organic layer was dried
3. concentrationconcentrated in vacuo
4. dissolutionthe resulting residue (2.40 g) was dissolved in AcOH (50 mL)
5. stirringstirred for 48 h at 60° C
6. temperatureAfter cooling to RT
7. customvolatiles were evaporated under reduced pressure
8. customthe residue was partitioned between EtOAc
9. washThe organic layer was washed with brine
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated in vacuo
12. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in DCM)

ORD record

ord-94ffb14b9d7f45d0b58091bf9e635ec8

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2