Ammonia → 2-(4-(1-Aminoethyl)-2-chlorophenyl)-2-methylpropanenitrile hydrochloride

HRID 419970Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 419970
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH3:14])([CH3:13])[C:11]#[N:12])=[C:6]([Cl:15])[CH:5]=1)(=O)[CH3:2].[BH4-].[Na+].Cl.CC(O)C.[NH3:23]>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-].O>[ClH:15].[NH2:23][CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH3:14])([CH3:13])[C:11]#[N:12])=[C:6]([Cl:15])[CH:5]=1)[CH3:2]

Komponenten

9

Edukt 5

HCID 222AmmoniaHCID 313Hydrochloric AcidHCID 3776IsopropanolHCID 4311764Sodium borohydrideHCID 582985122-(4-Acetyl-2-chlorophenyl)-2-methylpropanenitrile

Produkt 1

HCID 666489962-(4-(1-Aminoethyl)-2-chlorophenyl)-2-methylpropanenitrile hydrochlorideAusbeute 64 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11026Titanium isopropoxideKatalysatorHCID 887MethanolLösungsmittelHCID 962WaterLösungsmittel

Versuchsvorschrift

To a stirred solution of 2-(4-acetyl-2-chlorophenyl)-2-methylpropanenitrile (1.57 g, 7.08 mmol) in 7 M ammonia in methanol solution (35 mL) is added freshly distilled titanium (IV) isopropoxide (4.2 mL, 14.2 mmol). The reaction mixture is left stirring 18 h at room temperature. After cooling to 0° C., sodium borohydride (0.40 g, 10.6 mmol) is added and the reaction mixture is stirred at 0° C. until no more gas evolved and then at room temperature for 4 h. Water (40 mL) is then added and the titanium oxide is removed by filtration on a Buchner funnel. The filtrate is extracted with EtOAc (3×50 mL) and the combined organic layers are concentrated under reduced pressure. The resulting residue is dissolved in Et2O (200 mL), washed with brine, dried over anhydrous MgSO4 and filtered. To this solution is then added 5 N HCl in 2-propanol (1.8 mL, 8.85 mmol). The resulting precipitate is filtered on a Buchner funnel and dried to provide the desired 2-(4-(1-aminoethyl)-2-chlorophenyl)-2-methylpropanenitrile hydrochloride (1.17 g, 64%) as a white solid. 1H NMR (300 MHz, CD3OD): δ 7.69 (1H, d, J=10.7 Hz), 7.68 (1H, s), 7.52 (1H, dd, J=8.3, 2.0 Hz), 4.53 (1H, q, J=6.8 Hz), 1.90 (6H, s), 1.66 (3H, d, J=6.9 Hz). 13C NMR (75 MHz, CD3OD): δ 142.5, 140.2, 136.0, 132.0, 130.1, 127.9, 52.0, 37.8, 28.4, 21.3.

Aufarbeitung

  1. waitThe reaction mixture is left
  2. temperatureAfter cooling to 0° C.
  3. stirringthe reaction mixture is stirred at 0° C. until no more gas
  4. waitat room temperature for 4 h
  5. customthe titanium oxide is removed by filtration on a Buchner funnel
  6. extractionThe filtrate is extracted with EtOAc (3×50 mL)
  7. concentrationthe combined organic layers are concentrated under reduced pressure
  8. dissolutionThe resulting residue is dissolved in Et2O (200 mL)
  9. washwashed with brine
  10. dry with materialdried over anhydrous MgSO4
  11. filtrationfiltered
  12. filtrationThe resulting precipitate is filtered on a Buchner funnel
  13. customdried

Quellen und Nachweise

ORD-Eintrag
ord-087918b1ad1d49bbbdcb1661d013c7d6
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08093402B2

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