Water → (3aR,6aS)-2-[2,4-bis(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrole-5-carbaldehyde

HRID 1620645Notes

Reaction equation

HRID 1620645 reaction equation
Cl.[CH2:2]1[C@H:6]2[CH2:7][CH:8]([CH2:10][OH:11])[CH2:9][C@H:5]2[CH2:4][NH:3]1.C(=O)([O-])[O-].[K+].[K+].F[C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][C:20]=1[C:29]([F:32])([F:31])[F:30].O>CN(C=O)C>[F:26][C:25]([F:27])([F:28])[C:22]1[CH:21]=[C:20]([C:29]([F:30])([F:31])[F:32])[CH:19]=[CH:24][C:23]=1[N:3]1[CH2:4][C@@H:5]2[CH2:9][CH:8]([CH:10]=[O:11])[CH2:7][C@@H:6]2[CH2:2]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 203638951-Fluoro-2,4-bis(trifluoromethyl)benzeneHCID 86678792(3aR,6aS)-octahydrocyclopenta[c]pyrrol-5-ylmethanol hydrochloride

Product 1

HCID 86678811(3aR,6aS)-2-[2,4-bis(trifluoromethyl)phenyl]octahydrocyclopenta[c]pyrrole-5-carbaldehydeYield 12.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of (3aR,6aS)-octahydrocyclopenta[c]pyrrol-5-ylmethanol hydrochloride (862 mg) and potassium carbonate (1.68 g) in DMF (10 mL) was added 1-fluoro-2,4-bis(trifluoromethyl)benzene (1.24 g). The reaction mixture was stirred at 80° C. for 3 hr, water was added, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane). To a solution of the obtained oil (1.71 g) and triethylamine (2.03 mL) in DMSO (10 mL) and ethyl acetate (10 mL) was added sulfur trioxide pyridine complex (2.32 g) under cooling to 0° C. The reaction mixture was stirred at room temperature for 1 hr. To the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution, and the mixture was extracted with ethyl acetate. The extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (215 mg).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with water and saturated brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  6. additionTo a solution of the obtained oil (1.71 g) and triethylamine (2.03 mL) in DMSO (10 mL) and ethyl acetate (10 mL) was added sulfur trioxide pyridine complex (2.32 g)
  7. temperatureunder cooling to 0° C
  8. stirringThe reaction mixture was stirred at room temperature for 1 hr
  9. additionTo the reaction mixture was added saturated aqueous sodium hydrogen carbonate solution
  10. extractionthe mixture was extracted with ethyl acetate
  11. washThe extract was washed with water and saturated brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. customthe solvent was evaporated under reduced pressure
  14. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-23eb1c9cecb7484ebf8932e1c1f64487
Source dataset
uspto-grants-2014_07
Patent number
US08772277B2

Reaction notes

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