反应详情

A mixture of (R)-3-(2-aminophenylamino)piperidine-1-carboxylic acid tertbutyl ester (2.25 g, 7.72 mmol), (S)-2-benzyloxycarbonylaminopropionic acid (1.9 g, 8.49 mmol), HOAt (1.16 g, 8.49 mmol), N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (1.63 g, 8.49 mmol) and 4-methylmorpholine (1.87 mL, 16.98 mmol) in anhydrous DCM (50 mL) was stirred at RT for 1.5 h. The reaction mixture was diluted with DCM (200 mL) and washed with a 10% citric acid solution, followed by a saturated solution of NaHCO3 and then brine. The organic layer was then dried and concentrated in vacuo. The resulting residue was dissolved in AcOH (20 mL) and heated at 70° C. for 20 h and then at 80° C. for 2 h. After cooling to RT, volatiles were then removed in vacuo and the residue was dissolved in EtOAc (200 mL) and washed with a saturated solution of NaHCO3 (100 mL×2). The organic layer was then 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) affording (R)-3-[2-((S)-1-Benzyloxycarbonylaminoethyl)benzoimidazol-1-yl]piperidine-1-carboxylic acid tertbutyl ester as a white foam (2.75 g, 74%). LCMS: RT 3.16 min [M+H]+ 479.1.

1. washwashed with a 10% citric acid solution
2. customThe organic layer was then dried
3. concentrationconcentrated in vacuo
4. dissolutionThe resulting residue was dissolved in AcOH (20 mL)
5. temperatureheated at 70° C. for 20 h
6. waitat 80° C. for 2 h
7. temperatureAfter cooling to RT
8. customvolatiles were then removed in vacuo
9. dissolutionthe residue was dissolved in EtOAc (200 mL)
10. washwashed with a saturated solution of NaHCO3 (100 mL×2)
11. washThe organic layer was then washed with brine
12. dry with materialdried (Na2SO4)
13. concentrationconcentrated in vacuo
14. customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane)