反应详情

A mixture of (S)-2-tertbutoxycarbonylaminopropionic acid (480 mg, 2.53 mmol), 3-fluoro-N2-phenylbenzene-1,2-diamine (466 mg, 2.30 mmol), HOAt (345 mg, 2.53 mmol), 4-methylmorpholine (560 μL, 5.07 mmol) and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (486 mg, 2.53 mmol) in DCM (15 mL) was stirred at RT for 2 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 (1.0 g) was dissolved in AcOH (20 mL) and stirred for 18 h at 70° 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 water, followed by brine, then dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in DCM) affording [(S)-1-(7-Fluoro-1-phenyl-1H-benzoimidazol-2-yl)ethyl]carbamic acid tertbutyl ester as a yellow/orange oil (631 mg, 77%). LCMS: RT 3.64 min [M+H]+ 356.0.

1. customThe reaction mixture was then partitioned between additional DCM
2. customThe organic layer was dried
3. concentrationconcentrated in vacuo
4. dissolutionthe resulting residue (1.0 g) was dissolved in AcOH (20 mL)
5. stirringstirred for 18 h at 70° 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 water
10. dry with materialdried (Na2SO4)
11. concentrationconcentrated in vacuo
12. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-30% EtOAc in DCM)