Triethylsilane → Ethyl 5-bromo-3-(tetrahydro-2H-thiopyran-3-yl)-1H-indole-7-carboxylate

HRID 387268Notes

Reaction equation

HRID 387268 reaction equation
[S:1]1[CH2:6][CH2:5][CH2:4][C:3](=O)[CH2:2]1.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C.[Br:20][C:21]1[CH:22]=[C:23]2[C:27](=[C:28]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:29]=1)[NH:26][CH:25]=[CH:24]2.C([SiH](CC)CC)C>ClCCl>[Br:20][C:21]1[CH:22]=[C:23]2[C:27](=[C:28]([C:30]([O:32][CH2:33][CH3:34])=[O:31])[CH:29]=1)[NH:26][CH:25]=[C:24]2[CH:3]1[CH2:4][CH2:5][CH2:6][S:1][CH2:2]1

Participants

6

Reactant 4

HCID 12052TriethylsilaneHCID 65367Trimethylsilyl triflateHCID 140474Dihydro-2H-thiopyran-3(4H)-oneHCID 59332585Ethyl 5-bromo-1H-indole-7-carboxylate

Product 1

HCID 59332762Ethyl 5-bromo-3-(tetrahydro-2H-thiopyran-3-yl)-1H-indole-7-carboxylateYield 40.7%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

Dihydro-2H-thiopyran-3(4H)-one (0.217 g, 1.86 mmol) was dissolved in dichloromethane (23 mL) in an oven dried flask containing 3 Å molecular sieves and stirred under argon at 0° C. TMS-OTf (0.414 g, 1.86 mmol, 0.33 mL) was added slowly to the mixture over 10 min. Ethyl 5-bromo-1H-indole-7-carboxylate (0.5 g, 1.86 mmol) was dissolved in DCM (7 mL) and added to the reaction via syringe pump over 2 hours, after which it was stirred for 3 hours between 0 and 10° C. The reaction was cooled to 0° C. and triethylsilane (0.325 g, 0.44 mL, 2.8 mmol) was added all at once and the reaction was stirred at room temperature for 18 hours. The reaction was then quenched with a saturated sodium bicarbonate solution and extracted with DCM. The combined organics were washed with water. The combined aqueous layers were back-extracted with DCM. The combined organics were washed with brine, dried with MgSO4, and concentrated. The crude compound was purified on a Combiflash silica column with 5-25% EA/Hexane to give 0.279 g (40%) of the title compound.

Workup

  1. customdried flask
  2. additioncontaining 3 Å molecular sieves
  3. additionadded to the reaction via syringe pump over 2 hours
  4. stirringafter which it was stirred for 3 hours between 0 and 10° C
  5. temperatureThe reaction was cooled to 0° C.
  6. stirringwas stirred at room temperature for 18 hours
  7. customThe reaction was then quenched with a saturated sodium bicarbonate solution
  8. extractionextracted with DCM
  9. washThe combined organics were washed with water
  10. extractionThe combined aqueous layers were back-extracted with DCM
  11. washThe combined organics were washed with brine
  12. dry with materialdried with MgSO4
  13. concentrationconcentrated
  14. customThe crude compound was purified on a Combiflash silica column with 5-25% EA/Hexane

Sources & evidence

ORD record
ord-5e59aa506af4487fbc878bf5090278d0
Source dataset
uspto-grants-2013_02
Patent number
US08372875B2

Reaction notes

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