Cesium carbonate → 2-Bromo-6-{6-[2-(2-hydroxy-ethoxy)-1,1-dimethyl-ethyl]-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl}-benzaldehyde

HRID 2245723Notes

Reaction equation

HRID 2245723 reaction equation
[OH:1][CH2:2][C:3]([C:6]1[CH:7]=[C:8]2[C:13](=[CH:14][CH:15]=1)[C:12](=[O:16])[N:11](CC1C=CC(OC)=CC=1)[CH2:10][CH2:9]2)([CH3:5])[CH3:4].Br[C:27]1[CH:34]=[CH:33][CH:32]=[C:31]([Br:35])[C:28]=1[CH:29]=[O:30].C(=O)([O-])[O-].[Cs+].[Cs+].[O:42]1CCO[CH2:44][CH2:43]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].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:35][C:31]1[CH:32]=[CH:33][CH:34]=[C:27]([N:11]2[CH2:10][CH2:9][C:8]3[C:13](=[CH:14][CH:15]=[C:6]([C:3]([CH3:4])([CH3:5])[CH2:2][O:1][CH2:44][CH2:43][OH:42])[CH:7]=3)[C:12]2=[O:16])[C:28]=1[CH:29]=[O:30]

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 126486412,6-DibromobenzaldehydeHCID 671349876-(2-Hydroxy-1,1-dimethyl-ethyl)-2-(4-methoxy-benzyl)-3,4-dihydro-2H-isoquinolin-1-one

Product 1

HCID 592165302-Bromo-6-{6-[2-(2-hydroxy-ethoxy)-1,1-dimethyl-ethyl]-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl}-benzaldehyde

Reagents, catalysts & solvents 2

HCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)CatalystHCID 6505921(1E,4E)-1,5-diphenylpenta-1,4-dien-3-one; palladiumCatalyst

Procedure

Combined 0.131 g (0.5 mmol, 1 eq) 6-(2-Hydroxy-1,1-dimethyl-ethyl)-2-(4-methoxy-benzyl)-3,4-dihydro-2H-isoquinolin-1-one, 0.528 g 2,6-dibromobenzaldehyde (2 mmol, 4 eq), 6 mg Xantphos (0.01 mmol, 0.02 eq), 9 mg bis(dibenzylideneacetone)palladium (0.015 mmol, 0.03 eq), and 0.326 g Cesium Carbonate (1 mmol, 2.0 eq) in 5 ml dioxane, bubbled argon gas through the mixture for 1 minute, sealed the reaction vessel and heated at 100 C for 13 hours, filtered through a sintered glass funnel while hot, concentrated and purified on a silica gel column eluting with 5% to 10% Methanol in CH2Cl2 to give 148 mg. Rotovaped, chromatographed (10% to 30% ea in hexanes) to give a solid, 325 mg 2-Bromo-6-{6-[2-(2-hydroxy-ethoxy)-1,1-dimethyl-ethyl]-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl}-benzaldehyde. MS (ESI) 446.0 (M+H)+.

Workup

  1. customsealed the reaction vessel
  2. temperatureheated at 100 C for 13 hours
  3. filtrationfiltered through a sintered glass funnel while hot,
  4. concentrationconcentrated
  5. custompurified on a silica gel column
  6. washeluting with 5% to 10% Methanol in CH2Cl2
  7. customto give 148 mg
  8. customRotovaped, chromatographed (10% to 30% ea in hexanes)

Sources & evidence

ORD record
ord-c59cab4f59a44cb48fa8aac28285e9fe
Source dataset
uspto-grants-2010_03
Patent number
US07683064B2

Reaction notes

Loading…