Potassium Carbonate → {1-[2-(4-Fluorophenyl)ethyl]-piperidin-3-ylmethyl}carbamic Acid Benzyl Ester

HRID 896531Notes

Reaction equation

HRID 896531 reaction equation
Cl.[CH2:2]([O:9][C:10]([NH:12][CH2:13][CH:14]1[CH2:19][CH2:18][CH2:17][NH:16][CH2:15]1)=[O:11])[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1.[F:20][C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28]OS(C2C=CC(C)=CC=2)(=O)=O)=[CH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+]>C(=O)([O-])O.[Na+].CC(C)=O.O>[CH2:2]([O:9][C:10](=[O:11])[NH:12][CH2:13][CH:14]1[CH2:19][CH2:18][CH2:17][N:16]([CH2:28][CH2:27][C:24]2[CH:25]=[CH:26][C:21]([F:20])=[CH:22][CH:23]=2)[CH2:15]1)[C:3]1[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 17390106Benzeneethanol, 4-fluoro-, 1-(4-methylbenzenesulfonate)HCID 22350243Benzyl (piperidin-3-ylmethyl)carbamate hydrochloride

Product 1

HCID 69738345{1-[2-(4-Fluorophenyl)ethyl]-piperidin-3-ylmethyl}carbamic Acid Benzyl EsterYield 66%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolventHCID 962WaterSolventHCID 516892Sodium BicarbonateSolvent

Procedure

A solution of 3-(benzyloxycarbonylaminomethyl)-piperidine hydrochloride (199 mg, 690 μmol) was dissolved in aqueous sodium hydrogen carbonate and the solution was extracted with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. The residue was combined with toluene-4-sulfonic acid 2-(4-fluorophenyl)ethyl ester (97 mg, 690 μmol) and potassium carbonate (190 mg, 1.38 mmol) in acetone (15 mL) and the mixture was heated at reflux for 17 hours. The mixture was cooled, diluted with water, and extracted with ethyl acetate. The organic phase was dried over sodium sulfate and concentrated. The residue was purified by flash chromatography, eluting with ethyl acetate, to provide a white solid (140 mg, 66%). 1H NMR (300 MHz, CD3OD) δ7.30 (m, 5H), 7.22 (m, 2H), 6.99 (t, J=9 Hz, 2H), 5.07 (s, 2H), 3.1-2.7 (m, 5H), 2.55 (m, 2H), 2.00 (m, 1H), 1.8-1.5 (m, 4H), 0.98 (m, 1H). Mass spec (ES+) m/z 371.4 (M+H+, 100%).

Workup

  1. extractionthe solution was extracted with ethyl acetate
  2. dry with materialThe organic phase was dried over sodium sulfate
  3. concentrationconcentrated
  4. temperaturethe mixture was heated
  5. temperatureat reflux for 17 hours
  6. temperatureThe mixture was cooled
  7. extractionextracted with ethyl acetate
  8. dry with materialThe organic phase was dried over sodium sulfate
  9. concentrationconcentrated
  10. customThe residue was purified by flash chromatography
  11. washeluting with ethyl acetate

Sources & evidence

ORD record
ord-961feb7dcf704ab1acd87ab42cb3d5d7
Source dataset
uspto-grants-2005_07
Patent number
US06919356B2

Reaction notes

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