Potassium Carbonate → 5-Bromo-1-(3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)isoquinoline

HRID 2192469Notes

Reaction equation

HRID 2192469 reaction equation
[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6](C(C1C=CC=CC=1)=O)[CH:7]2[C:12]#N.BrC[CH2:24][CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28].[H-].[Na+].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl>[Br:1][C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[C:7]2[CH2:12][CH2:24][CH2:25][O:26][Si:27]([C:30]([CH3:33])([CH3:32])[CH3:31])([CH3:29])[CH3:28]

Participants

6

Reactant 4

HCID 11430Potassium CarbonateHCID 24758Sodium hydrideHCID 607486(3-Bromopropoxy)(tert-butyl)dimethylsilaneHCID 112677672-Benzoyl-5-bromo-1-cyano-1,2-dihydroisoquinoline

Product 1

HCID 581498995-Bromo-1-(3-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}propyl)isoquinolineYield 82.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-10 °C

Procedure

A dried round bottomed flask was charged with 5-bromo-2-(phenylcarbonyl)-1,2-dihydro-1-isoquinolinecarbonitrile (D10; 687 mg, 2.03 mmol) and dry, nitrogen purged N,N-dimethylformamide (DMF) (15 ml). The solution was cooled to −10° C. with stirring in an ice/methanol bath at which temperature the flask was evacuated. The flask was closed from the vacuum and allowed to warm to room temperature before the vacuum was re-introduced and the vessel then filled with nitrogen. (3-Bromopropoxy)-tert-butyldimethylsilane (available from Aldrich; 0.563 ml, 2.43 mmol) was added, the vessel purged with nitrogen three times and the solution cooled again to −10° C. To the solution was added sodium hydride (97 mg, 2.43 mmol) as a single portion. The mixture was held at −10° C. for 5 minutes before being allowed to warm to room temperature and stirred under nitrogen for 5 hours. To the mixture was added potassium carbonate (560 mg, 4.05 mmol). The slurry was warmed to 80° C. for 3 hours before being filtered through a plug of celite (ethyl acetate eluent). The organic layers were further diluted with ethyl acetate and partitioned with water (×3) then brine. The aqueous fractions were discarded and the organic layers passed through a hydrophobic frit before being concentrated in vacuo to give a tan oil. The oil was dissolved in DCM and purified by flash column chromatography on silica using 0% to 20% ethyl acetate in cyclohexane gradient elution. The relevant fractions were pooled and concentrated in vacuo to give the title compound as a yellow semi-solid (0.64 g).

Workup

  1. customdry
  2. customnitrogen purged N,N-dimethylformamide (DMF) (15 ml)
  3. customwas evacuated
  4. customThe flask was closed from the vacuum
  5. temperatureto warm to room temperature before the vacuum
  6. additionwas re-introduced
  7. additionthe vessel then filled with nitrogen
  8. customthe vessel purged with nitrogen three times
  9. temperaturethe solution cooled again to −10° C
  10. temperatureto warm to room temperature
  11. stirringstirred under nitrogen for 5 hours
  12. temperatureThe slurry was warmed to 80° C. for 3 hours
  13. filtrationbefore being filtered through a plug of celite (ethyl acetate eluent)
  14. additionThe organic layers were further diluted with ethyl acetate
  15. custompartitioned with water (×3)
  16. concentrationbefore being concentrated in vacuo
  17. customto give a tan oil
  18. custompurified by flash column chromatography on silica using 0% to 20% ethyl acetate in cyclohexane gradient elution
  19. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-a3a0a60291714daf8b461adad2f185ec
Source dataset
uspto-grants-2012_12
Patent number
US08329730B2

Reaction notes

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