Dimethyl Sulfoxide → methyl (1S,3R)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-methyl-1,2,3,4-tetrahydroisoquinoline-5-carboxylate

HRID 1854587Notes

Reaction equation

HRID 1854587 reaction equation
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][C@H:5]([CH2:13][O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[NH:6][C@H:7]2[CH3:12].[C:22](=[O:25])([O-])[O-:23].[Na+].[Na+].[C]=O.[CH3:30]S(C)=O>CO.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Si:15]([O:14][CH2:13][C@H:5]1[CH2:4][C:3]2[C:2]([C:22]([O:23][CH3:30])=[O:25])=[CH:11][CH:10]=[CH:9][C:8]=2[C@H:7]([CH3:12])[NH:6]1)([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16]

Participants

7

Reactant 4

HCID 679Dimethyl SulfoxideHCID 10340Sodium CarbonateHCID 118998349(1S,3R)-5-Bromo-3-(((tert-butyldimethylsilyl)oxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinolineHCID 178418416HCID 178418416, compound

Product 1

HCID 123884369methyl (1S,3R)-3-[[tert-butyl(dimethyl)silyl]oxymethyl]-1-methyl-1,2,3,4-tetrahydroisoquinoline-5-carboxylate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

In a glass pressure vessel, containing a magnetic stirrer bar, suspend (1S,3R)-5-bromo-3-((tert-butyldimethylsilyloxy)methyl)-1-methyl-1,2,3,4-tetrahydroisoquinoline (30 g, 81.0 mmol), palladium acetate (1.8 g, 8.1 mmol), bis-(1,3-diphenylphosphino)propane (6.7 g, 16.2 mmol) and sodium carbonate (34.3 g, 324.0 mmol) in a mixture of dimethyl sulfoxide (360 mL) and methanol (180 mL). Charge the vessel with carbon monoxide (410 kPa) and warm to 100° C. with stirring. Maintain temperature at 100° C. for 19 hours. Allow the mixture to cool to ambient temperature. Filter the resulting suspension and dilute the filtrate with methyl tert-butyl ether (1000 mL). Wash the solution with brine (3×500 mL). Dry over sodium sulfate, filter and concentrate under reduced pressure to yield the title compound as a dark orange oil (26.7 g, 76.4 mmol): MS (m/z): 350.0 (M+1).

Workup

  1. additionIn a glass pressure vessel, containing a magnetic stirrer bar
  2. temperatureMaintain temperature at 100° C. for 19 hours
  3. temperatureAllow the mixture to cool to ambient temperature
  4. filtrationFilter the resulting suspension
  5. additiondilute the filtrate with methyl tert-butyl ether (1000 mL)
  6. washWash the solution with brine (3×500 mL)
  7. dry with materialDry over sodium sulfate
  8. filtrationfilter
  9. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-c4302663e75b417ca1b524375efcaa99
Source dataset
uspto-grants-2015_02
Patent number
US08962654B2

Reaction notes

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