(Trifluoromethyl)trimethylsilane → 6-bromo-2-(4-methanesulfonylbenzyl)-4-phenyl-3-(2,2,2-trifluoro-1-hydroxyethyl)-2H-isoquinolin-1-one

HRID 750357Notes

Reaction equation

HRID 750357 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]1[CH:19]=[CH:18][C:17]([S:20]([CH3:23])(=[O:22])=[O:21])=[CH:16][CH:15]=1)[C:6]([CH:24]=[O:25])=[C:5]2[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.[F:32][C:33]([Si](C)(C)C)([F:35])[F:34].CCCC[N+](CCCC)(CCCC)CCCC.[F-]>C1COCC1>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]1[CH:15]=[CH:16][C:17]([S:20]([CH3:23])(=[O:21])=[O:22])=[CH:18][CH:19]=1)[C:6]([CH:24]([OH:25])[C:33]([F:35])([F:34])[F:32])=[C:5]2[C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1

Participants

5

Reactant 3

HCID 552549(Trifluoromethyl)trimethylsilaneHCID 2724141Tetrabutylammonium Fluoride2×HCID 230608166-Bromo-2-(4-methanesulfonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbaldehyde

Product 1

HCID 230605936-bromo-2-(4-methanesulfonylbenzyl)-4-phenyl-3-(2,2,2-trifluoro-1-hydroxyethyl)-2H-isoquinolin-1-oneYield 50.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Procedure

To a solution (5 ml) of 6-bromo-2-(4-methanesulfonylbenzyl)-1-oxo-4-phenyl-1,2-dihydroisoquinoline-3-carbaldehyde (500 mg) and (trifluoromethyl)trimethylsilane (170 mg) in THF was added a solution of tetra-N-butylammonium fluoride (1M, 0.03 ml) in THF at room temperature, and the mixture was stirred for 30 min. Then a solution (1M, 2 ml) of tetra-N-butylammonium fluoride in THF was added, and the mixture was stirred for 30 min. The reaction mixture was concentrated under reduced pressure and the residue was diluted with ethyl acetate. The organic layer was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (THF) and basic silica gel column chromatography (THF) and the crystals were washed with a mixture of ethyl acetate and diisopropyl ether, and recrystallized (MeOH-hexane) to give the title compound (290 mg).

Workup

  1. stirringthe mixture was stirred for 30 min
  2. concentrationThe reaction mixture was concentrated under reduced pressure
  3. additionthe residue was diluted with ethyl acetate
  4. washThe organic layer was washed with saturated aqueous sodium hydrogen carbonate, water and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe solvent was evaporated under reduced pressure
  7. customthe obtained residue was purified by silica gel column chromatography (THF) and basic silica gel column chromatography (THF)
  8. washthe crystals were washed with a mixture of ethyl acetate and diisopropyl ether
  9. customrecrystallized (MeOH-hexane)

Sources & evidence

ORD record
ord-37483b20dde946468bb14eb2945096b6
Source dataset
uspto-grants-2008_07
Patent number
US07402595B2

Reaction notes

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