4-tert-Butylbenzonitrile → 3-(4-(tert-butyl)phenyl)-6-methoxyisoquinolin-1(2H)-one

HRID 1852248

Reaction equation

HRID 1852248 reaction equation
C([N:3]([CH2:15][CH3:16])[C:4](=[O:14])[C:5]1[CH:10]=[CH:9][C:8]([O:11][CH3:12])=[CH:7][C:6]=1[CH3:13])C.[Li]CCCC.[C:22]([C:26]1[CH:33]=[CH:32]C(C#N)=[CH:28][CH:27]=1)([CH3:25])([CH3:24])[CH3:23]>C1COCC1>[C:22]([C:26]1[CH:33]=[CH:32][C:16]([C:15]2[NH:3][C:4](=[O:14])[C:5]3[C:6]([CH:13]=2)=[CH:7][C:8]([O:11][CH3:12])=[CH:9][CH:10]=3)=[CH:28][CH:27]=1)([CH3:25])([CH3:24])[CH3:23]

Participants

5

Reactant 3

HCID 778834-tert-ButylbenzonitrileHCID 11053218N,N-diethyl-4-methoxy-2-methyl-benzamideHCID 178418339Butyllithium

Product 1

HCID 709790183-(4-(tert-butyl)phenyl)-6-methoxyisoquinolin-1(2H)-oneYield 51.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of N,N-diethyl-4-methoxy-2-methylbenzamide (1 g, 4.52 mmol) in THF (10 ml) was added n-BuLi (2.82 ml, 4.52 mmol, in hexane) at −78° C. and stirred for 1 h. Then to this 4-(tert-butyl)benzonitrile (0.72 g, 4.52 mmol) was added at same temperature and allowed to warm to room temperature and continued the stirring for another 1 h at room temperature. The reaction mixture was quenched with saturated NH4Cl solution and extracted with EtOac (2*100 ml). The organic phase was washed with brine, dried on Na2SO4, and evaporated under reduced pressure to get crude compound. The crude compound was purified by silica gel chromatography (20% ethyl acetate in pet ether) to get desired compound (0.72 g, 46.7%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 11.26(s, 1H), 8.11-8.09 (d, J=8 Hz, 1H), 7.73-7.71 (d, J=8 Hz, 2H), 7.52-7.50 (d, J=8 Hz, 2H), 7.06 (s, 1H), 7.05-7.03 (d, J=8 Hz, 1H), 6.82 (s, 1H), 3.89 (s, 3H), 1.32 (s, 9H); MS: MS m/z 308.2 (M++1).

Workup

  1. customstirring for another 1 h
  2. customat room temperature
  3. customThe reaction mixture was quenched with saturated NH4Cl solution
  4. extractionextracted with EtOac (2*100 ml)
  5. washThe organic phase was washed with brine
  6. customdried on Na2SO4
  7. customevaporated under reduced pressure
  8. customto get crude compound
  9. customThe crude compound was purified by silica gel chromatography (20% ethyl acetate in pet ether)

Sources & evidence

ORD record
ord-4c73b52e940a4ebda95a89a788bad121
Source dataset
uspto-grants-2015_02
Patent number
US08957203B2

Linked notes

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