Potassium Carbonate → tert-Butyl 1-(2,2,2-trifluoroethyl)piperidin-4-ylcarbamate

HRID 1280570Notes

Reaction equation

HRID 1280570 reaction equation
[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([CH3:4])([CH3:3])[CH3:2].ClC(Cl)(Cl)S(O[CH2:21][C:22]([F:25])([F:24])[F:23])(=O)=O.C(=O)([O-])[O-].[K+].[K+]>CC(C)=O>[C:1]([O:5][C:6](=[O:14])[NH:7][CH:8]1[CH2:13][CH2:12][N:11]([CH2:21][C:22]([F:25])([F:24])[F:23])[CH2:10][CH2:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 900272,2,2-Trifluoroethyl trichloromethanesulphonateHCID 7238334-(N-Boc-amino)piperidine

Product 1

HCID 22562166tert-Butyl 1-(2,2,2-trifluoroethyl)piperidin-4-ylcarbamate

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Piperidin-4-yl-carbamic acid tert-butyl ester (commercially available from ASTATECH) (5 g, 24.96 mmol), 2,2,2,-trifluoroethyl trichloromethane sulfonate (7.03 g, 1 equivalent), and potassium carbonate (4.1 g, 1.2 eq) were taken up in acetone (80 mL) and heated at reflux with stirring for 17 hours. The solvent was removed under reduced pressure at 40° C. and ethyl acetate and water were added to the residue. The layers were partitioned and then separated. The organic layer was washed with water and brine, dried over magnesium sulfate, filtered, and concentrated to give a dark colored solid. Purification by chromatography on silica gel using 15% ethyl acetate in hexanes as the eluant gave [1-(2,2,2-trifluoroethyl)piperidin-4-yl]-carbamic acid tert-butyl ester (4.45 g) as an off-white powder, m.p. 99.2-99.8° C., (M+H)+=283.

Workup

  1. temperatureheated
  2. temperatureat reflux
  3. customThe solvent was removed under reduced pressure at 40° C.
  4. additionethyl acetate and water were added to the residue
  5. customThe layers were partitioned
  6. customseparated
  7. washThe organic layer was washed with water and brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a dark colored solid
  12. customPurification by chromatography on silica gel using 15% ethyl acetate in hexanes as the eluant

Sources & evidence

ORD record
ord-ffa8cf0607494a4c99c6c5de11eda8fe
Source dataset
uspto-grants-2002_09
Patent number
US06451804B1

Reaction notes

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