Sodium hydride → HCID 66671460, compound

HRID 446551Notes

Reaction equation

HRID 446551 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][CH:12]=1)[C:9](=[O:13])[NH:8][CH2:7][CH2:6]2.Br[CH2:15][CH2:16][CH2:17][O:18][Si](C(C)(C)C)(C)C.[H-].[Na+].[Cl-].[NH4+].[F-].C([N+](CCCC)(CCCC)CCCC)CCC.O1CCCC1>CN(C)C=O.C(OCC)(=O)C>[OH:18][CH2:17][CH2:16][CH2:15][N:8]1[CH2:7][CH2:6][C:5]2[C:10](=[CH:11][CH:12]=[C:3]([O:2][CH3:1])[CH:4]=2)[C:9]1=[O:13]

Participants

8

Reactant 5

HCID 24758Sodium hydrideHCID 25517Ammonium Chloride2×HCID 607486(3-Bromopropoxy)(tert-butyl)dimethylsilaneHCID 106073926-methoxy-3,4-dihydroisoquinolin-1(2H)-oneHCID 11078149TBAF tetrahydrofuran

Product 1

HCID 66671460HCID 66671460, compoundYield 145.4%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

6-Methoxy-3,4-dihydroisoquinolin-1(2H)-one (1.0 g, 5.64 mmol) was dissolved in N,N-dimethylformamide (15 mL), (3-bromopropoxy)(tert-butyl)dimethylsilane (2.62 mL, 11.3 mmol) and 55% sodium hydride (259 mg, 5.93 mmol) were added under ice cooling, and the mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. After the reaction was completed, saturated aqueous ammonium chloride was added to the reaction mixture under ice cooling, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The resulting residue was dissolved in tetrahydrofuran (5 mL), a 1.0 M tetrabutylammonium fluoride-tetrahydrofuran solution (22.5 mL, 22.5 mmol) was added under ice cooling, and the mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours. After the reaction was completed, saturated aqueous ammonium chloride was added to the reaction mixture under ice cooling, and ethyl acetate was further added to separate the layers. The resulting organic layer was separated, washed with saturated sodium chloride solution, and then dried with anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:methanol, 10:1, v/v) to give the title compound (1.93 g; yield, 100%) as a colorless oily substance.

Workup

  1. customto separate the layers
  2. customThe resulting organic layer was separated
  3. washwashed with saturated sodium chloride solution
  4. dry with materialdried with anhydrous sodium sulfate
  5. customthe solvent was evaporated under reduced pressure
  6. dissolutionThe resulting residue was dissolved in tetrahydrofuran (5 mL)
  7. stirringthe mixture was stirred at room temperature under a nitrogen atmosphere for 2 hours
  8. customto separate the layers
  9. customThe resulting organic layer was separated
  10. washwashed with saturated sodium chloride solution
  11. dry with materialdried with anhydrous sodium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe residue was purified by silica gel column chromatography (ethyl acetate

Sources & evidence

ORD record
ord-b61cd260582d4a38b3826c86f80a730f
Source dataset
uspto-grants-2013_07
Patent number
US08476253B2

Reaction notes

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