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

HRID 242805

Reaktionsgleichung

Reaktionsgleichung von HRID 242805
[C:1]1([NH:7][C:8]2[C:9]([NH2:14])=[CH:10][CH:11]=[CH:12][CH:13]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:15]([O:19][C:20]([NH:22][C@@H:23]([CH2:27][CH3:28])[C:24](O)=O)=[O:21])([CH3:18])([CH3:17])[CH3:16].C1C=NC2N(O)N=NC=2C=1.Cl.CN(C)CCCN=C=NCC.CN1CCOCC1>C(Cl)Cl>[C:15]([O:19][C:20](=[O:21])[NH:22][C@H:23]([C:24]1[N:7]([C:1]2[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=2)[C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=2[N:14]=1)[CH2:27][CH3:28])([CH3:18])([CH3:17])[CH3:16]

Komponenten

7

Edukt 5

HCID 79724-MethylmorpholineHCID 68297N-Phenyl-o-phenylenediamineHCID 181649HOAtHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 2755934(S)-2-((tert)-Butoxycarbonyl)amino)butanoic acid

Produkt 1

HCID 68157215[(S)-1-(1-Phenyl-1H-benzoimidazol-2-yl)propyl]carbamic acid tertbutyl esterAusbeute 92,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Versuchsvorschrift

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

Aufarbeitung

  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)

Quellen und Nachweise

ORD-Eintrag
ord-e663501622394e2f965154abc3884fdf
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08653089B2

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