Potassium Carbonate → 1-[2-(5-hydroxy-5-trifluoromethyl-5-H-indeno[1,2-b]pyridin-3-yloxy)-ethyl]-pyrrolidin-2-one

HRID 541153Notes

Reaction equation

HRID 541153 reaction equation
[O:1]=[C:2]1[CH2:6][CH2:5][CH2:4][N:3]1[CH2:7][CH2:8][O:9][C:10]1[CH:11]=[C:12]2[C:22](=[O:23])[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[C:13]2=[N:14][CH:15]=1.C(=O)([O-])[O-].[K+].[K+].C[Si](C)(C)[C:32]([F:35])([F:34])[F:33].[F-].C([N+](CCCC)(CCCC)CCCC)CCC>O1CCCC1.C(OCC)(=O)C.C(O)(=O)C.CN(C)C=O>[OH:23][C:22]1([C:32]([F:35])([F:34])[F:33])[C:12]2[C:13](=[N:14][CH:15]=[C:10]([O:9][CH2:8][CH2:7][N:3]3[CH2:4][CH2:5][CH2:6][C:2]3=[O:1])[CH:11]=2)[C:16]2[C:21]1=[CH:20][CH:19]=[CH:18][CH:17]=2

Participants

9

Reactant 4

HCID 11430Potassium CarbonateHCID 552549(Trifluoromethyl)trimethylsilane2×HCID 2724141Tetrabutylammonium FluorideHCID 594925093-[2-(2-Oxo-pyrrolidin-1-yl)-ethoxy]-indeno[1,2-b]pyridin-5-one

Product 1

HCID 594927191-[2-(5-hydroxy-5-trifluoromethyl-5-H-indeno[1,2-b]pyridin-3-yloxy)-ethyl]-pyrrolidin-2-oneYield 68%

Reagents, catalysts & solvents 4

HCID 176Acetic AcidSolventHCID 6228DimethylformamideSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

3-[2-(2-oxo-pyrrolidin-1-yl)-ethoxy]-indeno[1,2-b]pyridin-5-one (0.0376 g) and potassium carbonate (0.001 g) were mixed with dimethylformamide (1.0 ml), and the mixture was stirred at 0° C. To this mixture was added trimethyl(trifluoromethyl)silane (0.035 ml), and the mixture was stirred at 0° C. for 1 hr. Trimethyl(trifluoromethyl)silane (0.018 ml) was further added, and the mixture was stirred at 0° C. for 1 hr. To the reaction mixture was added acetic acid (0.010 ml), then a 1M solution (0.12 ml) of tetrabutylammonium fluoride in tetrahydrofuran was added, and the mixture was stirred at 0° C. for 30 min. To the reaction mixture was added ethyl acetate (20 ml), and the mixture was placed in a separatory funnel. The organic layer was washed 3 times with water (10 ml) and once with saturated brine (10 ml). The organic layer was dried over anhydrous sodium sulfate, and filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by preparative thin layer chromatography (silica gel, eluent: n-hexane/ethyl acetate=7/3) to give the title compound (0.0389 g, 68%).

Workup

  1. stirringthe mixture was stirred at 0° C. for 1 hr
  2. stirringthe mixture was stirred at 0° C. for 1 hr
  3. stirringthe mixture was stirred at 0° C. for 30 min
  4. customthe mixture was placed in a separatory funnel
  5. washThe organic layer was washed 3 times with water (10 ml)
  6. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by preparative thin layer chromatography (silica gel, eluent: n-hexane/ethyl acetate=7/3)

Sources & evidence

ORD record
ord-d182853f58d4483697f72c953ca4364e
Source dataset
uspto-grants-2014_10
Patent number
US08871934B2

Reaction notes

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