Iodine → 1-(1-Benzylpiperidin-4-yl)-2-(2-fluorophenyl)ethanol

HRID 914804

Reaction equation

HRID 914804 reaction equation
[Mg].II.[F:4][C:5]1[CH:12]=[CH:11][CH:10]=[CH:9][C:6]=1[CH2:7]Cl.[CH2:13]([N:20]1[CH2:25][CH2:24][CH:23]([CH:26]=[O:27])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1.[Cl-].[NH4+]>C(OCC)C.C(OCC)(=O)C>[CH2:13]([N:20]1[CH2:25][CH2:24][CH:23]([CH:26]([OH:27])[CH2:7][C:6]2[CH:9]=[CH:10][CH:11]=[CH:12][C:5]=2[F:4])[CH2:22][CH2:21]1)[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1

Participants

8

Reactant 5

HCID 807IodineHCID 9580Benzene, 1-(chloromethyl)-2-fluoro-HCID 25517Ammonium ChlorideHCID 895841-Benzylpiperidine-4-carbaldehydeHCID 5462224Magnesium

Product 1

HCID 222481731-(1-Benzylpiperidin-4-yl)-2-(2-fluorophenyl)ethanolYield 62%

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolvent3×HCID 8857Ethyl AcetateSolvent

Procedure

After suspending 1.84 g of magnesium in 20 ml of diethyl ether, a catalytic amount of iodine was added, a portion of a diethyl ether solution (70 ml) containing 9.97 g of 2-fluorobenzyl chloride was added dropwise while stirring, and the mixture was heated to initiate the reaction. The remaining solution was then added dropwise at a rate to maintain reflux. After 10 minutes, the mixture was cooled on ice, a diethyl ether solution (70 ml) containing 15.4 g of 1-benzyl-4-piperidinecarboxaldehyde [CAS No. 22065-85-6] was added dropwise, and stirring was continued for 20 minutes. Saturated aqueous ammonium chloride solution was added to the reaction solution and extraction was performed with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate, and then the solvent was distilled off under reduced pressure. The residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate) to obtain the title compound (13.4 g, 62% yield).

Workup

  1. additionwas added dropwise
  2. temperaturethe mixture was heated
  3. customthe reaction
  4. additionThe remaining solution was then added dropwise at a rate
  5. temperatureto maintain
  6. temperaturereflux
  7. temperaturethe mixture was cooled on ice
  8. addition22065-85-6] was added dropwise
  9. stirringstirring
  10. waitwas continued for 20 minutes
  11. washThe organic layer was washed with brine
  12. dry with materialdried over anhydrous magnesium sulfate
  13. distillationthe solvent was distilled off under reduced pressure
  14. customThe residue was purified by NH silica gel column chromatography (solvent: n-hexane/ethyl acetate)

Sources & evidence

ORD record
ord-2f1eb9591f3944218bac0bfbdd3eb106
Source dataset
uspto-grants-2007_09
Patent number
US07265108B2

Linked notes

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