Ammonia → 2-[4-(1-Aminoethyl)-2-methylphenyl]-2-methylpropanenitrile

HRID 603132Notes

Reaction equation

HRID 603132 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH3:14])([CH3:13])[C:11]#[N:12])=[C:6]([CH3:15])[CH:5]=1)(=O)[CH3:2].[BH4-].[Na+].O.[NH3:19]>CO.CC(C)[O-].[Ti+4].CC(C)[O-].CC(C)[O-].CC(C)[O-]>[NH2:19][CH:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH3:14])([CH3:13])[C:11]#[N:12])=[C:6]([CH3:15])[CH:5]=1)[CH3:2]

Participants

7

Reactant 4

HCID 222AmmoniaHCID 962WaterHCID 4311764Sodium borohydrideHCID 582984812-(4-Acetyl-2-methylphenyl)-2-methylpropanenitrile

Product 1

HCID 582984602-[4-(1-Aminoethyl)-2-methylphenyl]-2-methylpropanenitrileYield 75%

Reagents, catalysts & solvents 2

HCID 11026Titanium isopropoxideCatalystHCID 887MethanolSolvent

Procedure

To a stirred solution of 2-(4-acetyl-2-methylphenyl)-2-methylpropanenitrile (1.77 g, 8.80 mmol) in 7 M ammonia in MeOH (45 mL) is added freshly distilled titanium (IV) isopropoxide (5.20 mL, 17.6 mmol). The reaction mixture is left stirring 18 h at room temperature. After cooling to 0° C., sodium borohydride (500 mg, 13.2 mmol) is added and the reaction mixture stirred at 0° C. until no more gas evolved and then at room temperature 3 h. Water (25 mL) is then added and the titanium oxide removed by filtration on a Buchner funnel. The filtrate is extracted with EtOAc (3×100 mL) (brine (10 mL) is added to help separation between both layers) and the combined organic layers are concentrated under reduced pressure. The resulting crude product (which contained water) is dissolved in Et2O (75 mL), washed with brine, dried over MgSO4 and filtered. 5-6 N HCl in 2-propanol (2.2 mL) is slowly added to the well-stirred filtrate. The resulting white precipitate is filtered on a Buchner funnel and dried in vacuo to provide the expected product 2-[4-(1-aminoethyl)-2-methylphenyl]-2-methylpropanenitrile (1.58 g, 75%) as a white solid. 1H NMR (300 MHz, CD3OD): δ 7.55 (1H, d, J=8.0 Hz), 7.44-7.37 (2H, m), 4.97 (3H, s), 4.52 (1H, q, J=6.9 Hz), 2.75 (3H, s), 1.86 (6H, s), 1.69 (3H, d, J=6.9 Hz).

Workup

  1. waitThe reaction mixture is left
  2. temperatureAfter cooling to 0° C.
  3. stirringthe reaction mixture stirred at 0° C. until no more gas
  4. customat room temperature
  5. custom3 h
  6. customthe titanium oxide removed by filtration on a Buchner funnel
  7. extractionThe filtrate is extracted with EtOAc (3×100 mL) (brine (10 mL)
  8. additionis added
  9. customseparation between both layers) and the combined organic layers
  10. concentrationare concentrated under reduced pressure
  11. dissolutionThe resulting crude product (which contained water) is dissolved in Et2O (75 mL)
  12. washwashed with brine
  13. dry with materialdried over MgSO4
  14. filtrationfiltered
  15. addition5-6 N HCl in 2-propanol (2.2 mL) is slowly added to the well-stirred filtrate
  16. filtrationThe resulting white precipitate is filtered on a Buchner funnel
  17. customdried in vacuo

Sources & evidence

ORD record
ord-f293222105264b148c4f464fd6c35888
Source dataset
uspto-grants-2011_03
Patent number
US07906654B2

Reaction notes

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