反应详情

A mixture of N-phenylbenzene-1,2-diamine (1.0 g, 5.43 mmol), (S)-2-tertbutoxycarbonylaminobutyric acid (1.21 g, 5.97 mmol), HOAt (813 mg, 5.97 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.15 g, 5.97 mmol) and 4-methylmorpholine (1.31 mL, 11.95 mmol) in DCM (20 mL) was stirred at RT for 2 h. The crude reaction mixture was diluted with DCM (100 mL), then washed with a saturated solution of NaHCO3, followed by brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was dissolved in AcOH (20 mL) and heated to 70° C. for 18 h. After cooling to RT, volatiles were evaporated under reduced pressure and the residue was dissolved in EtOAc (150 mL) and washed with a saturated solution of NaHCO3. The organic layer was then washed with brine, dried (Na2SO4) and then concentrated in vacuo. The resulting residue was absorbed onto HM-N and purified twice by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) affording [(S)-1-(1-Phenyl-1H-benzoimidazol-2-yl)propyl]carbamic acid tertbutyl ester (1.76 g). LCMS: RT 3.23 min [M+H-tBu]+ 352.2

1. customThe crude reaction mixture
2. washwashed with a saturated solution of NaHCO3
3. dry with materialdried (Na2SO4)
4. concentrationconcentrated in vacuo
5. dissolutionThe resulting residue was dissolved in AcOH (20 mL)
6. temperatureheated to 70° C. for 18 h
7. temperatureAfter cooling to RT
8. customvolatiles were evaporated under reduced pressure
9. dissolutionthe residue was dissolved in EtOAc (150 mL)
10. washwashed with a saturated solution of NaHCO3
11. washThe organic layer was then washed with brine
12. dry with materialdried (Na2SO4)
13. concentrationconcentrated in vacuo
14. customThe resulting residue was absorbed onto HM-N
15. custompurified twice by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane)