Water → 4-[2-Fluoro-3-(methylsulfonyl)phenyl]-1-propylpiperidine

HRID 2358032Notes

Reaction equation

HRID 2358032 reaction equation
[F:1][C:2]1[C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]1.C(=O)([O-])[O-].[K+].[K+].I[CH2:25][CH2:26][CH3:27].O>C(#N)C>[F:1][C:2]1[C:7]([S:8]([CH3:11])(=[O:10])=[O:9])=[CH:6][CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][CH2:16][N:15]([CH2:25][CH2:26][CH3:27])[CH2:14][CH2:13]1

Participants

6

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 336431-IodopropaneHCID 574480384-[2-Fluoro-3-(methylsulfonyl)phenyl]piperidine

Product 1

HCID 115149334-[2-Fluoro-3-(methylsulfonyl)phenyl]-1-propylpiperidineYield 79.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 4-[2-fluoro-3-(methylsulfonyl)phenyl]piperidine (0.4 g, 1.55 mmol) in acetonitrile (40 ml) was added potassium carbonate (0.3 g, 2.17 mmol) and 1-iodopropane (0.151 ml, 1.55 mmol) and the mixture was heated at reflux for 15 h. The mixture was cooled to ambient temperature and water (50 ml) was added. The aqueous residue was extracted with ethylacetate (3×50 ml) and the combined organic phases was dried, concentrated, and purified by flash column chromatography (ethylacetate/methanol, 1:1) to give the title compound (0.37 g, 79%). The amine was converted to the hydrochloric acid salt and recrystallized from ethanol/diethyl ether: M.p. 255-257° C. MS m/z (relative intensity, 70 eV) 299 (M+, 2), 271 (16), 270 (bp), 147 (9) 133 (10).

Workup

  1. temperaturethe mixture was heated
  2. temperatureat reflux for 15 h
  3. extractionThe aqueous residue was extracted with ethylacetate (3×50 ml)
  4. customthe combined organic phases was dried
  5. concentrationconcentrated
  6. custompurified by flash column chromatography (ethylacetate/methanol, 1:1)

Sources & evidence

ORD record
ord-7831ed8929eb4321baedd0a89b6e33e8
Source dataset
uspto-grants-2010_07
Patent number
US07763639B2

Reaction notes

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