Potassium Phosphate, Tribasic → cis-2,2,2-Trifluoro-1-(6-methyl-2,3,4,4a,9,9a-hexahydro-indeno[2,1-b]pyridin-1-yl)-ethanone

HRID 455370Notes

Reaction equation

HRID 455370 reaction equation
[F:1][C:2]([F:27])([F:26])[C:3]([N:5]1[CH2:10][CH2:9][CH2:8][C@@H:7]2[C:11]3[CH:12]=[C:13](OS(C(F)(F)F)(=O)=O)[CH:14]=[CH:15][C:16]=3[CH2:17][C@H:6]12)=[O:4].[CH3:28]B1OB(C)OB(C)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.O1CCOCC1>[F:1][C:2]([F:27])([F:26])[C:3]([N:5]1[CH2:10][CH2:9][CH2:8][C@@H:7]2[C:11]3[CH:12]=[C:13]([CH3:28])[CH:14]=[CH:15][C:16]=3[CH2:17][C@H:6]12)=[O:4]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 574072Trimethylboroxine3×HCID 58294405trifluoro-methanesulfonic acid cis-1-(2,2,2-trifluoro-acetyl)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridin-6-yl ester

Product 1

HCID 58294400cis-2,2,2-Trifluoro-1-(6-methyl-2,3,4,4a,9,9a-hexahydro-indeno[2,1-b]pyridin-1-yl)-ethanone

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalyst3×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

Tetrakis(triphenylphosphine)palladium(0) (17 mg) is added to a flask charged with a stir bar, trifluoromethanesulfonic acid cis-1-(2,2,2-trifluoro-acetyl)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridin-6-yl ester (200 mg), trimethylboroxine (81 μL), K3PO4 (0.15 g), and 1,4-dioxane (4 mL) under argon atmosphere at room temperature. The reaction mixture is heated to 100° C. and stirred at this temperature overnight. Another portion of trimethylboroxine (40 μL) and tetrakis(triphenylphosphine)palladium(0) (17 mg) is then added and stirring is continued at 100° C. The addition of further amounts of trimethylboroxine and tetrakis(triphenylphosphine)palladium(0) is repeated after each 6 h of stirring until the starting material is completely consumed. After cooling to room temperature, water is added and the resulting mixture is extracted with ethyl acetate. The combined extract is dried (Na2SO4) and concentrated and the residue is chromatographed on silica gel (dichloromethane/methanol 1:0→9:1) to give the title compound. Yield: 50 mg (37% of theory); LC (method 1): tR=4.62 min; Mass spectrum (ESI+): m/z=284 [M+H]+.

Workup

  1. additioncharged with a stir bar
  2. customat room temperature
  3. stirringstirring
  4. customis continued at 100° C
  5. waitis repeated after each 6 h
  6. stirringof stirring until the starting material
  7. customis completely consumed
  8. temperatureAfter cooling to room temperature
  9. additionwater is added
  10. extractionthe resulting mixture is extracted with ethyl acetate
  11. extractionThe combined extract
  12. dry with materialis dried (Na2SO4)
  13. concentrationconcentrated
  14. customthe residue is chromatographed on silica gel (dichloromethane/methanol 1:0→9:1)

Sources & evidence

ORD record
ord-40dc514852b947d6925c3791a2dfe25a
Source dataset
uspto-grants-2013_07
Patent number
US08497281B2

Reaction notes

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