Ammonia → 2-[4-(Aminomethyl)-3-methylphenyl]-2-methylpropanenitrile

HRID 419974Notes

Reaction equation

HRID 419974 reaction equation
[CH:1]([C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH3:13])([CH3:12])[C:10]#[N:11])=[CH:5][C:4]=1[CH3:14])=O.[BH4-].[Na+].[NH3:17]>CO.CC(O[Ti](OC(C)C)(OC(C)C)OC(C)C)C>[NH2:17][CH2:1][C:3]1[CH:8]=[CH:7][C:6]([C:9]([CH3:13])([CH3:12])[C:10]#[N:11])=[CH:5][C:4]=1[CH3:14]

Participants

6

Reactant 3

HCID 222AmmoniaHCID 4311764Sodium borohydrideHCID 582984532-(4-Formyl-3-methylphenyl)-2-methylpropanenitrile

Product 1

HCID 582984482-[4-(Aminomethyl)-3-methylphenyl]-2-methylpropanenitrileYield 87%

Reagents, catalysts & solvents 2

HCID 178460666HCID 178460666, compoundCatalystHCID 887MethanolSolvent

Procedure

2-(4-formyl-3-methylphenyl)-2-methylpropanenitrile 1.89 g, 10.2 mmol) is dissolved in 50 ml of 7M NH3 in MeOH. Ti(OiPr)4 (6 mmol, 20 mmol) is added and the mixture stirred for 3 hours at room temperature. NaBH4 (0.6 g, 15 mmol) is added and the reaction left at room temperature overnight. The mixture is quenched by the addition of 25 ml of NH4OH 2 M. The resulting precipitate is filtered off and washed with EtOAc. Phases are separated, the organic phase is dried over magnesium sulfate, filtered and evaporated to dryness, giving 2-[4-(aminomethyl)-3-methylphenyl]-2-methylpropanenitrile (1.325 g, 7.09 mmol, 87%). The crude product is used without further purification. 1H NMR (400 MHz, DMSO-D6) δ 1.64 (s, 6H, first rotamer) 1.65 (s, 6H, second rotamer) 2.28 (s, 3H, first rotamer) 2.29 (s, 3H, second rotamer) 3.32 (broad s, 2 H) 3.67 (s, 2H, first rotamer) 3.68 (s, 2H, second rotamer) 7.24-7.27 (m, 1H) 7.28 (s, 1H) 7.36-7.40 (m, 1H).

Workup

  1. waitthe reaction left at room temperature overnight
  2. customThe mixture is quenched by the addition of 25 ml of NH4OH 2 M
  3. filtrationThe resulting precipitate is filtered off
  4. washwashed with EtOAc
  5. customPhases are separated
  6. dry with materialthe organic phase is dried over magnesium sulfate
  7. filtrationfiltered
  8. customevaporated to dryness

Sources & evidence

ORD record
ord-d4fbeb144e584750975fa69cf8243bb4
Source dataset
uspto-grants-2012_01
Patent number
US08093402B2

Reaction notes

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