Tetrahydrofuran → HCID 58117448, compound

HRID 1406406Notes

Reaction equation

HRID 1406406 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:17]1[C:18](=[O:34])[N:19]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:33])([CH3:32])[CH3:31])[CH:20]=[C:21]([N+:23]([O-])=O)[CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].O1CCCC1.[F-].[K+]>O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[CH:10]=[C:9]1[C:17]1[C:18](=[O:34])[N:19]([CH2:26][O:27][CH2:28][CH2:29][Si:30]([CH3:31])([CH3:32])[CH3:33])[CH:20]=[C:21]([NH2:23])[CH:22]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 3

HCID 8028TetrahydrofuranHCID 522689Potassium FluorideHCID 58117303HCID 58117303, compound2×

Product 1

HCID 58117448HCID 58117448, compoundYield 67%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Procedure

A round bottom flask was charged with intermediate (6b), 2-[5-nitro-2-oxo-1-(2-trimethylsilanyl-ethoxymethyl)-1,2-dihydro-pyridin-3-yl]-indole-1-carboxylic acid tert-butyl ester (0.485 g, 1 mmol), tetrahydrofuran (5 mL) and palladium acetate (11 mg, 5 mol %). The flask was sealed and purged with nitrogen. While purging the flask with nitrogen, a solution of potassium fluoride (116 mg, 2 mmol) in water (2 mL), which had been thoroughly degassed, was added via syringe. The nitrogen inlet was removed and replaced with a balloon of nitrogen. Poly(methylhydrosiloxane) (0.44 mL) was added drop wise and the reaction was stirred at ambient temperature for 18 hours. The reaction mixture was diluted with dichloromethane (20 mL) and aqueous saturated sodium bicarbonate solution (20 mL). The organic layer was separated, filtered through a bed of celite and concentrated in vacuo. The resultant crude product was purified by flash chromatography on SiO2 eluting with hexane—50% ethyl acetate/hexane (gradient) to afford the desired title compound as a brown solid 0.308 g, 67%.

Workup

  1. customThe flask was sealed
  2. custompurged with nitrogen
  3. customWhile purging the flask with nitrogen
  4. additionwas added via syringe
  5. customThe nitrogen inlet was removed
  6. additionPoly(methylhydrosiloxane) (0.44 mL) was added drop wise
  7. additionThe reaction mixture was diluted with dichloromethane (20 mL) and aqueous saturated sodium bicarbonate solution (20 mL)
  8. customThe organic layer was separated
  9. filtrationfiltered through a bed of celite and
  10. concentrationconcentrated in vacuo
  11. customThe resultant crude product was purified by flash chromatography on SiO2 eluting with hexane—50% ethyl acetate/hexane (gradient)

Sources & evidence

ORD record
ord-ed897caf008d4812b605bbc19090fb8b
Source dataset
uspto-grants-2014_12
Patent number
US08916591B2

Reaction notes

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