Diisopropylamine → 3-(4-Bromophenyl)-5-methyl-1(2h)-isoquinolinone

HRID 717090Notes

Reaction equation

HRID 717090 reaction equation
C(NC(C)C)(C)C.[Li]CCCC.C([N:15]([CH2:26][CH3:27])[C:16](=[O:25])[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH3:23])[C:18]=1[CH3:24])C.[Br:28][C:29]1[CH:36]=[CH:35]C(C#N)=[CH:31][CH:30]=1>C1COCC1>[Br:28][C:29]1[CH:36]=[CH:35][C:27]([C:26]2[NH:15][C:16](=[O:25])[C:17]3[C:18]([CH:24]=2)=[C:19]([CH3:23])[CH:20]=[CH:21][CH:22]=3)=[CH:31][CH:30]=1

Participants

6

Reactant 4

HCID 7912DiisopropylamineHCID 12162Benzonitrile, 4-bromo-HCID 15621069N,N-Diethyl-2,3-dimethylbenzamideHCID 178418339Butyllithium

Product 1

HCID 762845543-(4-Bromophenyl)-5-methyl-1(2h)-isoquinolinoneYield 58.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To N,N-diisopropylamine (2.54 mL, 18 mmol) in anhydrous THF (15 mL), under N2 at −78° C. was added n-BuLi dropwise (2.5M in n-hexanes, 7.2 mL, 18 mmol) and the reaction mixture maintained at this temperature for 30 minutes. A solution of N,N-diethyl-2,3-dimethyl-benzamide (1.23 g, 6 mmol) in anhydrous THF (15 mL) was added dropwise to give a deep red solution. After 20 minutes at −78° C., 4-bromobenzonitrile (1.09 g, 6 mmol) in anhydrous THF (15 mL) was added dropwise and the reaction mixture allowed to stir at this temperature for 2.5 h. The reaction mixture was quenched by adding dropwise onto ice, upon which a pale yellow solid precipitated out. The solid was triturated with iso-hexane/EtOAc (2:1), filtered and dried in vacuo to afford 3-(4-bromo-phenyl)-5-methyl-2H-isoquinolin-1-one as a pale yellow solid (1.1 g, 58%).

Workup

  1. temperaturethe reaction mixture maintained at this temperature for 30 minutes
  2. customto give a deep red solution
  3. customThe reaction mixture was quenched
  4. additionby adding dropwise onto ice, upon which a pale yellow solid
  5. customprecipitated out
  6. customThe solid was triturated with iso-hexane/EtOAc (2:1)
  7. filtrationfiltered
  8. customdried in vacuo

Sources & evidence

ORD record
ord-83fe2691a5fc457cb75bccd3a2e300b5
Source dataset
uspto-grants-2015_11
Patent number
US09193689B2

Reaction notes

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