Methyl iodide → 6-Bromo-2-methyl-1,2-dihydroisoquinolin-1-one

HRID 2403051Notes

Reaction equation

HRID 2403051 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8]([OH:12])=[N:7][CH:6]=[CH:5]2.I[CH3:14].[OH-].[Na+]>[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.C(OCC)C>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH3:14])[CH:6]=[CH:5]2

Participants

7

Reactant 3

HCID 6328Methyl iodideHCID 14798Sodium HydroxideHCID 178517609HCID 178517609, compound

Product 1

HCID 231581786-Bromo-2-methyl-1,2-dihydroisoquinolin-1-oneYield 70%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 1140TolueneSolventHCID 3283Diethyl EtherSolvent

Procedure

6-Bromo-1-hydroxyisoquinoline (140 mg, 0.63 mmol, 1.0 equiv), tetrabutylammonium bromide (30 mg, 0.09 mmol, 0.15 equiv), and iodomethane (50 uL, 0.75 mmol, 1.2 equiv) were combined in toluene (10 mL) and treated with 50% aq. NaOH (2 mL), and the resulting was mixture stirred rapidly at ambient temperature. After an additional 14 h at room temperature, the mixture was diluted with diethyl ether and washed with water, saturated NaHCO3, and brine. The organic phase was dried over Na2SO4 and concentrated to give a white solid of 6-bromo-2-methylisoquinolin-1-one (104 mg, 0.44 mmol, 70%). This crude material was taken forward without further purification and converted, via Methods 1 and 2, to compound 1 (45 mg, 38%) and isolated as a beige solid. [M-H]-=202.1 m/z. Activity: B

Workup

  1. washwashed with water, saturated NaHCO3, and brine
  2. dry with materialThe organic phase was dried over Na2SO4
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-b4f68472e1164af3b380d4fdd86808d4
Source dataset
uspto-grants-2014_08
Patent number
US08802064B2

Reaction notes

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