Potassium Carbonate → 4-(4-Methoxy-benzylamino)-nicotinonitrile

HRID 2264906Notes

Reaction equation

HRID 2264906 reaction equation
Cl[C:2]1[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][CH:3]=1.[CH3:10][O:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16][NH2:17])=[CH:14][CH:13]=1.C(=O)([O-])[O-].[K+].[K+]>CC(O)C>[CH3:10][O:11][C:12]1[CH:19]=[CH:18][C:15]([CH2:16][NH:17][C:2]2[C:7]([C:8]#[N:9])=[CH:6][N:5]=[CH:4][CH:3]=2)=[CH:14][CH:13]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 754524-MethoxybenzylamineHCID 134111124-Chloro-nicotinonitrile

Product 1

HCID 595966574-(4-Methoxy-benzylamino)-nicotinonitrileYield 93.2%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

A solution of 4-chloronicotinonitrile (1.00 g, 7.22 mmol), 4-methoxybenzylamine (1.03 ml, 7.94 mmol) and potassium carbonate (1.20 g, 8.66 mmol) in propan-2-ol (20 mL) was heated under reflux for 18 hours. The solvent was concentrated in vacuo and the residue partitioned between EtOAc (150 mL) and water (50 mL). The organic phase was dried (Na2SO4), filtered and evaporated to give a brown oil. The oil was pre-adsorbed onto H-MN and purified by flash column chromatography (Si-PPC, cyclohexane:EtOAc, gradient 80:20 to 0:100) to provide the title compound as a white solid (1.61 g, 93%). 1H NMR (CDCl3, 300 MHz) 8.46 (d, J=0.7 Hz, 1H), 8.30 (dd, J=6.1 Hz, 0.7 Hz, 1H), 7.24 (dd, J=8.6 Hz, 2.1 Hz, 2H), 6.92 (dd, J=8.6 Hz, 2.1 Hz, 2H), 6.55 (d, J=6.1 Hz, 1H), 5.35 (br t, 1H), 4.40 (d, J=5.6 Hz, 2H), 3.82 (s, 3H).

Workup

  1. temperatureunder reflux for 18 hours
  2. concentrationThe solvent was concentrated in vacuo
  3. customthe residue partitioned between EtOAc (150 mL) and water (50 mL)
  4. dry with materialThe organic phase was dried (Na2SO4)
  5. filtrationfiltered
  6. customevaporated
  7. customto give a brown oil
  8. custompurified by flash column chromatography (Si-PPC, cyclohexane:EtOAc, gradient 80:20 to 0:100)

Sources & evidence

ORD record
ord-b11acea26a1c47e8a2e6f58f71b80bd7
Source dataset
uspto-grants-2010_12
Patent number
US07855216B2

Reaction notes

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