Potassium Carbonate → 2-(3-bromo-2-methylphenyl)-3,4-dihydroisoquinolin-1(2H)-one

HRID 661884

Reaction equation

HRID 661884 reaction equation
Br[C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([Br:8])[C:3]=1[CH3:9].[C:10]1(=[O:20])[C:19]2[C:14](=[CH:15][CH:16]=[CH:17][CH:18]=2)[CH2:13][CH2:12][NH:11]1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C(Cl)Cl.[Cu]I>[Br:8][C:4]1[C:3]([CH3:9])=[C:2]([N:11]2[CH2:12][CH2:13][C:14]3[C:19](=[CH:18][CH:17]=[CH:16][CH:15]=3)[C:10]2=[O:20])[CH:7]=[CH:6][CH:5]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 346812,6-Dibromotoluene2×HCID 1508963,4-dihydroisoquinolin-1(2H)-one2×

Product 1

HCID 593751142-(3-bromo-2-methylphenyl)-3,4-dihydroisoquinolin-1(2H)-oneYield 66.1%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
150 °C

Procedure

Step 2 A mixture of 1,3-dibromo-2-methylbenzene (340 mg, 1.359 mmol), 3,4-dihydroisoquinolin-1(2H)-one (100 mg, 0.679 mmol) and potassium carbonate (94 mg, 0.679 mmol) in DMSO (2 mL) was purged with nitrogen, treated with copper (I) iodide (25.9 mg, 0.136 mmol) and heated at 150° C. for 3.5 h. The mixture was combined with that from a second reaction using 1,3-dibromo-2-methylbenzene (2.59 g, 10.36 mmol) and 3,4-dihydroisoquinolin-1(2H)-one (508 mg, 3.45 mmol), diluted with DCM and filtered through Celite. The filtrate was washed with 5% aqueous ammonium hydroxide, dried and concentrated. The residue was purified by column chromatography (eluting with hexane-EtOAc) to provide 2-(3-bromo-2-methylphenyl)-3,4-dihydroisoquinolin-1(2H)-one as a yellow solid (142 mg, 11%). 1H NMR (400 MHz, chloroform-d) δ 8.15 (1H, dd, J=7.70, 1.10 Hz), 7.55 (1H, dd, J=7.92, 1.10 Hz), 7.46-7.51 (1H, m), 7.37-7.42 (1H, m), 7.24-7.28 (1H, m), 7.17-7.21 (1H, m), 7.09-7.16 (1H, m), 3.95 (1H, ddd, J=12.21, 10.12, 4.73 Hz), 3.73 (1 H, ddd, J=11.94, 6.33, 5.28 Hz), 3.26 (1H, ddd, J=15.74, 10.23, 5.28 Hz), 3.06-3.14 (1H, m), 2.36 (3H, s). Mass spectrum m/z 316, 318 (M+H)+.

Workup

  1. customwas purged with nitrogen
  2. customfrom a second reaction
  3. filtrationfiltered through Celite
  4. washThe filtrate was washed with 5% aqueous ammonium hydroxide
  5. customdried
  6. concentrationconcentrated
  7. customThe residue was purified by column chromatography (eluting with hexane-EtOAc)

Sources & evidence

ORD record
ord-98e0e8da894c45a68096c12098af0b37
Source dataset
uspto-grants-2011_12
Patent number
US08084620B2

Linked notes

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