Cesium carbonate → 2-Bromo-6-(6-tert-butyl-1-oxo-1H-isoquinolin-2-yl)-benzaldehyde

HRID 2069816Notes

Reaction equation

HRID 2069816 reaction equation
[C:1]([C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[C:11](=[O:15])[NH:10][CH:9]=[CH:8]2)([CH3:4])([CH3:3])[CH3:2].[Br:16][C:17]1[CH:24]=[CH:23][CH:22]=[C:21](Br)[C:18]=1[CH:19]=[O:20].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd]>[Br:16][C:17]1[CH:24]=[CH:23][CH:22]=[C:21]([N:10]2[CH:9]=[CH:8][C:7]3[C:12](=[CH:13][CH:14]=[C:5]([C:1]([CH3:4])([CH3:2])[CH3:3])[CH:6]=3)[C:11]2=[O:15])[C:18]=1[CH:19]=[O:20]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 126486412,6-DibromobenzaldehydeHCID 595638256-tert-butyl-2H-isoquinolin-1-one

Product 1

HCID 592164492-Bromo-6-(6-tert-butyl-1-oxo-1H-isoquinolin-2-yl)-benzaldehyde

Reagents, catalysts & solvents 2

HCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

6-tert-Butyl-2H-isoquinolin-1-one (272 mg, 1.35 mmol), 2,6-Dibromo-benzaldehyde (891 mg, 2.5 eq), xanthphos (35 mg, 0.045 eq) and cesium carbonate (616 mg, 1.4 eq) were taken up in dioxane (2.7 mL). Then nitrogen was bubbled through the solution for 10 minutes before adding bis(dibenzylideneacetone)palladium (23 mg, 0.03 eq). The resulting mixture was stirred at 100° C. overnight. By TLC and LC/MS there was no desired product observed. Next added copper iodide (55 mg, 0.02 eq) and cesium carbonate (320 mg, 0.73 eq) and more dioxane (4 mL). The resulting mixture was heated to 100° C. with stirring for 30 hours and by TLC the reaction was now complete. After cooling to room temperature, ethyl acetate (175 mL) and water (50 mL) were added. The layers were partitioned, and separated. The organice layer was then washed with water (3×50 mL) and finally with brine (1×50 mL) before drying over magnesium sulfate, filtering and concentrating. Purification on silica gel eluting with a step-wise gradient of 5% ethyl acetate to 20% ethyl acetate in hexanes gave the title compound as a light tan powder (215 mg). MS (ESI) 346.0 (M+H)+.

Workup

  1. customThen nitrogen was bubbled through the solution for 10 minutes

Sources & evidence

ORD record
ord-0e4a48b4bfe1469f9d61a52cb1633546
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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