Chloroform → 2-Bromo-6-(6-cyclopropyl-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-benzaldehyde

HRID 2069790Notes

Reaction equation

HRID 2069790 reaction equation
[CH:1]1([C:4]2[CH:5]=[C:6]3[C:11](=[CH:12][CH:13]=2)[C:10](=[O:14])[NH:9][CH2:8][CH2:7]3)[CH2:3][CH2:2]1.[Br:15][C:16]1[CH:23]=[CH:22][CH:21]=[C:20](Br)[C:17]=1[CH:18]=[O:19].C(Cl)(Cl)Cl.C(=O)([O-])[O-].[Cs+].[Cs+]>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].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>[Br:15][C:16]1[CH:23]=[CH:22][CH:21]=[C:20]([N:9]2[CH2:8][CH2:7][C:6]3[C:11](=[CH:12][CH:13]=[C:4]([CH:1]4[CH2:3][CH2:2]4)[CH:5]=3)[C:10]2=[O:14])[C:17]=1[CH:18]=[O:19]

Participants

7

Reactant 4

HCID 6212ChloroformHCID 10796Cesium carbonateHCID 126486412,6-DibromobenzaldehydeHCID 574241176-cyclopropyl-3,4-dihydro-2H-isoquinolin-1-one

Product 1

HCID 592164432-Bromo-6-(6-cyclopropyl-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-benzaldehydeYield 351.1%

Reagents, catalysts & solvents 2

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst

Conditions

Temperature
110 °C

Procedure

A round bottom flask was charged with 6-Cyclopropyl-3,4-dihydro-2H-isoquinolin-1-one (13.4 g, 5 mmol), 2,6-Dibromo-benzaldehyde (47.5 g, 72.0 mmol), Pd2 (dba)3.CHCl3 (660 mg, 0.72 mmol), xanthphos (832 mg, 1.44 mmol), and cesium carbonate (46.8 g, 144 mmol). The vial was flushed with argon, 140 mL of dioxane was added, and the reaction mixture was heated at 110° C. for 4 h. The reaction mixture was cooled to rt and 30 mL of water and 60 mL of ethyl acetate were added before filtering over Solkaflok. The organic phase was separated and washed with brine followed by drying over Na2SO4. After filtration, the solvent was removed and the brown mass obtained was triturated with methylene chloride and diethyl ether to afford 6.5 grams of 2-Bromo-6-(6-cyclopropyl-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl)-benzaldehyde. A second crop of 7.5 grams of material was collected by addition of more diethyl ether. MS (ESI) 370.0 (M+H)+.

Workup

  1. customThe vial was flushed with argon, 140 mL of dioxane
  2. additionwas added
  3. temperatureThe reaction mixture was cooled to rt
  4. addition30 mL of water and 60 mL of ethyl acetate were added
  5. filtrationbefore filtering over Solkaflok
  6. customThe organic phase was separated
  7. washwashed with brine
  8. dry with materialby drying over Na2SO4
  9. filtrationAfter filtration
  10. customthe solvent was removed
  11. customthe brown mass obtained
  12. customwas triturated with methylene chloride and diethyl ether

Sources & evidence

ORD record
ord-3f654af4e76d45d09efe34e9c2b30698
Source dataset
uspto-grants-2012_10
Patent number
US08299077B2

Reaction notes

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