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

HRID 589511

Reaction equation

HRID 589511 reaction equation
Br[C:2]1[CH:9]=[CH:8][CH:7]=[C:6]([Br:10])[C:3]=1[CH:4]=[O:5].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+].[OH:59][C:60]([C:63]1[CH:64]=[C:65]2[C:70](=[CH:71][CH:72]=1)[C:69](=[O:73])[NH:68][CH2:67][CH2:66]2)([CH3:62])[CH3:61]>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.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O>[Br:10][C:6]1[CH:7]=[CH:8][CH:9]=[C:2]([N:68]2[CH2:67][CH2:66][C:65]3[C:70](=[CH:71][CH:72]=[C:63]([C:60]([OH:59])([CH3:61])[CH3:62])[CH:64]=3)[C:69]2=[O:73])[C:3]=1[CH:4]=[O:5]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 126486412,6-DibromobenzaldehydeHCID 592165246-(1-Hydroxy-1-methyl-ethyl)-3,4-dihydro-2H-isoquinolin-1-one

Product 1

HCID 867310022-Bromo-6-[6-(1-hydroxy-1-methyl-ethyl)-1-oxo-3,4-dihydro-1H-isoquinolin-2-yl]-benzaldehyde

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Procedure

To a mixture of 2,6-dibromo-benzaldehyde (1.60 g, 6.06 mmol), Pd2(dba)3 (222 mg, 0.243 mmol), xantphos (210 mg, 0.364 mmol), and Cs2CO3 (2.77 g, 8.49 mmol) in dioxane (60 ml) under argon was added 6-(1-hydroxy-1-methyl-ethyl)-3,4-dihydro-2H-isoquinolin-1-one (US2009/0306041) (995 mg, 4.85 mmol). The resulting mixture was refluxed overnight. After cooling down to r.t., water was added, and the mixture was extracted three times with EtOAc. The combined organic layers were dried, filtered, and evaporated to dryness. The crude product was purified by flash chromatography (silica gel, cyclohexane/EtOAC gradient) to yield Intermediate 42.

Workup

  1. temperatureThe resulting mixture was refluxed overnight
  2. extractionthe mixture was extracted three times with EtOAc
  3. customThe combined organic layers were dried
  4. filtrationfiltered
  5. customevaporated to dryness
  6. customThe crude product was purified by flash chromatography (silica gel, cyclohexane/EtOAC gradient)

Sources & evidence

ORD record
ord-90af4d69beb0411eb58739cf642e7ca0
Source dataset
uspto-grants-2016_01
Patent number
US09233111B2

Linked notes

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