Ammonium Hydroxide → 2-[4-(1-Aminoethyl)-3-methylphenyl]-2-methylpropanenitrile

HRID 419958Notes

Reaction equation

HRID 419958 reaction equation
[C:1]([C:4]1[CH:9]=[CH:8][C:7]([C:10]([CH3:14])([CH3:13])[C:11]#[N:12])=[CH:6][C:5]=1[CH3:15])(=O)[CH3:2].[BH4-].[Na+].[OH-].[NH4+:19]>N.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])=[CH:6][C:5]=1[CH3:15])[CH3:2]

Participants

7

Reactant 3

HCID 14923Ammonium HydroxideHCID 4311764Sodium borohydrideHCID 582984882-(4-Acetyl-3-methylphenyl)-2-methylpropanenitrile

Product 1

HCID 582984892-[4-(1-Aminoethyl)-3-methylphenyl]-2-methylpropanenitrileYield 99%

Reagents, catalysts & solvents 3

HCID 11026Titanium isopropoxideCatalystHCID 222AmmoniaSolventHCID 887MethanolSolvent

Procedure

To a stirred solution of 2-(4-acetyl-3-methylphenyl)-2-methylpropanenitrile (1.0 g, 4.97 mmol) in 7 M ammonia in MeOH (40 mL) is added titanium (IV) isopropoxide (3.0 g, 9.95 mmol). The reaction mixture is left stirring 24 h at room temperature. After cooling to 0° C., sodium borohydride (1.0 g, 19.9 mmol) is added and the reaction mixture stirred and left to warm-up to room temperature 1 h. Conc. ammonium hydroxide (15 mL) is then added and the titanium oxide is removed by filtration and is washed with ethyl acetate. The filtrate is extracted with EtOAc (2×100 mL) and the combined organic layers are dried over MgSO4, filtered and concentrated under reduced to provide the expected product 2-[4-(1-aminoethyl)-3-methylphenyl]-2 methylpropanenitrile (1.0 g, 99%) as a clear yellow oil. 1H NMR (400 MHz, CHLOROFORM-D) δ ppm 1.33 (d, J=6.64 Hz, 3H) 1.44 (s, 2H) 1.70 (s, 6H) 2.36 (s, 3H) 4.34 (q, J=6.44 Hz, 1 H) 7.22 (d, J=1.95 Hz, 1H) 7.28 (dd, J=8.20, 2.15 Hz, 1H) 7.48 (d, J=8.20 Hz, 1H)

Workup

  1. waitThe reaction mixture is left
  2. temperatureAfter cooling to 0° C.
  3. stirringthe reaction mixture stirred
  4. waitleft
  5. temperatureto warm-up to room temperature 1 h
  6. customthe titanium oxide is removed by filtration
  7. washis washed with ethyl acetate
  8. extractionThe filtrate is extracted with EtOAc (2×100 mL)
  9. dry with materialthe combined organic layers are dried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated under reduced

Sources & evidence

ORD record
ord-b0083a034e024aa080b7cd8e799ca0a8
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

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