Ethyl Acetate → HCID 58495795, compound

HRID 2359342Notes

Reaction equation

HRID 2359342 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[CH:8]=[N:7][CH:6]=[C:5]2[OH:12].C(N(C(C)C)CC)(C)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:51]([O:54][CH2:55][CH3:56])(=[O:53])C.[CH3:57][Si:58](C)([CH3:62])[CH2:59]CO>CN(C)C=O.[Pd](Cl)Cl.CO>[OH:12][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([C:51]([O:54][CH2:55][CH2:56][Si:58]([CH3:62])([CH3:59])[CH3:57])=[O:53])[CH:3]=2)[CH:8]=[N:7][CH:6]=1

Participants

9

Reactant 5

HCID 8857Ethyl AcetateHCID 180132-(Trimethylsilyl)ethanolHCID 812191,3-Bis(diphenylphosphino)propaneHCID 81531DiisopropylethylamineHCID 573461516-Bromoisoquinolin-4-ol

Product 1

HCID 58495795HCID 58495795, compoundYield 85.4%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolventHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

6-Bromo-4-hydroxyisoquinoline (15.7 g, 70.0 mmol) produced in Example 15 (15a) was dissolved in dimethylformamide (100 mL), to which 2-trimethylsilylethanol (100 mL), diisopropylethylamine (27.1 g, 210 mmol), 1,3-bis(diphenylphosphino)propane (8.67 g, 21.0 mmol), and palladium chloride (3.72 g, 21.0 mmol) were then added, followed by stirring at 60° C. for eight hours under a carbon monoxide atmosphere. The solvent was distilled off under reduced pressure. Water was added to the residue thus obtained, and the resulting mixture was extracted with dichloromethane. The resulting organic layer was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue thus obtained was purified by silica gel column chromatography ((a mixed solvent of hexane:ethyl acetate-1:1):methanol, 100:0-70:30, V/V) to give the desired title compound (17.3 g, yield 85.4%).

Workup

  1. additionwere then added
  2. distillationThe solvent was distilled off under reduced pressure
  3. additionWater was added to the residue
  4. customthus obtained
  5. extractionthe resulting mixture was extracted with dichloromethane
  6. dry with materialThe resulting organic layer was dried over anhydrous sodium sulfate
  7. distillationthe solvent was distilled off under reduced pressure
  8. customThe residue thus obtained
  9. customwas purified by silica gel column chromatography ((a mixed solvent of hexane

Sources & evidence

ORD record
ord-84b0134895654a2eae2dfc9a2cb4ffe4
Source dataset
uspto-grants-2014_04
Patent number
US08685981B2

Reaction notes

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