4-(2-Oxiranylmethoxy)benzenecarbonitrile → 4-{3-[(3-Benzyl-3-azabicyclo[3.2.1]oct-8-yl)(methyl)amino]-2-hydroxypropoxy}benzonitrile

HRID 411519Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 411519
[CH2:1]([N:8]1[CH2:14][CH:13]2[CH:15]([NH:16][CH3:17])[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C[Al](C)C.[O:22]1[CH2:24][CH:23]1[CH2:25][O:26][C:27]1[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][CH:28]=1>ClCCl>[CH2:1]([N:8]1[CH2:14][CH:13]2[CH:15]([N:16]([CH3:17])[CH2:24][CH:23]([OH:22])[CH2:25][O:26][C:27]3[CH:34]=[CH:33][C:30]([C:31]#[N:32])=[CH:29][CH:28]=3)[CH:10]([CH2:11][CH2:12]2)[CH2:9]1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Komponenten

5

Edukt 3

HCID 27643014-(2-Oxiranylmethoxy)benzenecarbonitrileHCID 16682925TrimethylaluminumHCID 185410303-benzyl-N-methyl-3-azabicyclo[3.2.1]octan-8-amine

Produkt 1

HCID 185408994-{3-[(3-Benzyl-3-azabicyclo[3.2.1]oct-8-yl)(methyl)amino]-2-hydroxypropoxy}benzonitrileAusbeute 66 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Reaktionsbedingungen

Temperatur
25 °C

Versuchsvorschrift

To a solution of 3-benzyl-N-methyl-3-azabicyclo[3.2.1]octan-8-amine (Preparation B; 3.72 g, 16.1 mmol) in dichloromethane (80 mL) at 25° C. under nitrogen was added trimethylaluminum (8.05 mL of 2.0 M in hexane, 16.1 mmol). After stirring at 25° C. for 30 min, 4-(2-oxiranyl-methoxy)benzonitrile (see step (i) above; 2.83 g, 16.1 mmol) was added in one portion, and the mixture was stirred overnight. The mixture was quenched with 6 N NaOH (13.5 mL) and stirred 1 h. Water (100 mL) was added, and the aqueous layer was extracted with dichloromethane (3×100 mL). The combined organic extracts were dried (Na2SO4), filtered and concentrated in vacuo to afford an oil. The residue was chromatographed on silica gel, eluting with dichloromethane:methanol (98:2), to afford 4.30 g (66%) of the sub-title compound as a colorless oil.

Aufarbeitung

  1. stirringthe mixture was stirred overnight
  2. customThe mixture was quenched with 6 N NaOH (13.5 mL)
  3. stirringstirred 1 h
  4. additionWater (100 mL) was added
  5. extractionthe aqueous layer was extracted with dichloromethane (3×100 mL)
  6. dry with materialThe combined organic extracts were dried (Na2SO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customto afford an oil
  10. customThe residue was chromatographed on silica gel
  11. washeluting with dichloromethane:methanol (98:2)

Quellen und Nachweise

ORD-Eintrag
ord-da50a9c901144305afed45d238547caa
Quelldatensatz
uspto-grants-2003_05
Patentnummer
US06559162B2

Notizen zur Reaktion

Wird geladen…