Reaktion #329987

Reaktionsgleichung

N-phenylbenzene-1,2-diamine

(S)-2-tertbutoxycarbonylaminobutyric acid

HOAt

N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride

4-methylmorpholine

→

[(S)-1-(1-Phenyl-1H-benzoimidazol-2-yl)propyl]carbamic acid tertbutyl ester

Ausbeute 92.2%

Lösungsmittel

DCM

DCM

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe crude reaction mixture
2. 2
   Waschenwashed with a saturated solution of NaHCO3
3. 3
   Trocknendried (Na2SO4)
4. 4
   Einengenconcentrated in vacuo
5. 5
   workup.DISSOLUTIONThe resulting residue was dissolved in AcOH (20 mL)
6. 6
   Temperaturheated to 70° C. for 18 h
7. 7
   TemperaturAfter cooling to RT
8. 8
   Sonstigevolatiles were evaporated under reduced pressure
9. 9
   workup.DISSOLUTIONthe residue was dissolved in EtOAc (150 mL)
10. 10
    Waschenwashed with a saturated solution of NaHCO3
11. 11
    WaschenThe organic layer was then washed with brine
12. 12
    Trocknendried (Na2SO4)
13. 13
    Einengenconcentrated in vacuo
14. 14
    SonstigeThe resulting residue was absorbed onto HM-N
15. 15
    Sonstigepurified twice by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane)

Vorschrift

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

Quelle