Hydrochloric Acid → 1-(1,2,3,4-Tetrahydroisoquinolin-6-yl)ethan-1-one

HRID 1713083Notes

Reaction equation

HRID 1713083 reaction equation
C(OC([N:8]1[CH2:17][CH2:16][C:15]2[C:10](=[CH:11][CH:12]=[C:13](OS(C(F)(F)F)(=O)=O)[CH:14]=2)[CH2:9]1)=O)(C)(C)C.[CH2:26]([O:30]C=C)[CH2:27]CC.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(OC=C)=C.Cl.C(=O)([O-])[O-].[Na+].[Na+]>CN(C=O)C.CCOC(C)=O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH2:9]1[C:10]2[C:15](=[CH:14][C:13]([C:26](=[O:30])[CH3:27])=[CH:12][CH:11]=2)[CH2:16][CH2:17][NH:8]1

Participants

11

Reactant 6

HCID 313Hydrochloric AcidHCID 8024Vinyl etherHCID 8108Butyl vinyl etherHCID 10340Sodium CarbonateHCID 812191,3-Bis(diphenylphosphino)propaneHCID 10091216Tert-butyl 6-(trifluoromethylsulfonyloxy)-3,4-dihydroisoquinoline-2(1H)-carboxylate

Product 1

HCID 574205651-(1,2,3,4-Tetrahydroisoquinolin-6-yl)ethan-1-one

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
80 °C

Procedure

To a stirred solution of 6-trifluoromethanesulfonyloxy-3,4-dihydro-1H-isoquinoline-2-carboxylicacid tert-butyl ester (3.81 g, 10 mmol) in dry DMF (30 ml) are added n-butylvinyl ether (6.01 g, 60 mmol, 6.0 eq.), TEA (1.67 ml, 12 mmol, 1.2 eq.), 1,3-bis(diphenylphosphino)propane (144 mg, 0.276 mmol, 0.0276 eq.), and palladium acetate (56.1 mg, 0.25 mmol, 0.025 eq.) under nitrogen. The resulting mixture is stirred at 80° C. for 7 hr. Water (100 ml) is added to quench the reaction, and the mixture is extracted with EtOAc (30 ml×3). The combined organic layer is washed with water and brine, dried over sodium sulfate, and concentrated. The crude product is purified through silica gel flash chromatography (hexane/EtOAc 10:1) to give a mixture of the vinyl ether and the ketone product, which is dissolved in EtOAc (50 ml), and then treated with concentrated hydrochloric acid (3.0 ml). The mixture is stirred at rt for 2 hr, and then basified with saturated sodium carbonate solution. The organic phase is collected, and the aqueous phase is extracted with EtOAc twice. The combined organic phase is dried with sodium sulfate and concentrated to give the title compound. MS (+VE) m/z 176.1 (M++1).

Workup

  1. customto quench
  2. customthe reaction
  3. extractionthe mixture is extracted with EtOAc (30 ml×3)
  4. washThe combined organic layer is washed with water and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationconcentrated
  7. customThe crude product is purified through silica gel flash chromatography (hexane/EtOAc 10:1)
  8. customto give
  9. stirringThe mixture is stirred at rt for 2 hr
  10. customThe organic phase is collected
  11. extractionthe aqueous phase is extracted with EtOAc twice
  12. dry with materialThe combined organic phase is dried with sodium sulfate
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-f97aab371e5a4d5d8d276e513fd246c6
Source dataset
uspto-grants-2010_09
Patent number
US07795262B2

Reaction notes

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