Iodine → Tert-butyl 4-(2-fluoro-5-iodo-4-methoxyphenyl)piperidine-1-carboxylate

HRID 607048Notes

Reaction equation

HRID 607048 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[CH:5]=[CH:4][C:3]=1[CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1.[I:23]I>CO.S([O-])([O-])(=O)=O.[Ag+2]>[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([I:23])=[CH:4][C:3]=1[CH:10]1[CH2:15][CH2:14][N:13]([C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[CH2:12][CH2:11]1

Participants

5

Reactant 2

HCID 807IodineHCID 67066012Tert-butyl 4-(2-fluoro-4-methoxyphenyl)piperidine-1-carboxylate

Product 1

HCID 67066021Tert-butyl 4-(2-fluoro-5-iodo-4-methoxyphenyl)piperidine-1-carboxylate

Reagents, catalysts & solvents 2

HCID 178418844HCID 178418844, compoundCatalystHCID 887MethanolSolvent

Procedure

A stirred mixture of tert-butyl 4-(2-fluoro-4-methoxyphenyl)piperidine-1-carboxylate (Step A; 255 mg; 0.825 mmol) in MeOH. (15 mL) was treated with iodine (345 mg; 1.107 mmol) and silver sulfate (281 mg; 1.107 mmol). The reaction was stirred at room temperature for 2 h. The reaction was filtered through Celite and the filtrate was concentrated in vacuo. The residue was redissolved in ether (50 mL) and washed with H2O (50 mL). The aqueous layer was extracted with ether (3×50 mL) and the combined extracts were washed with brine (50 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-10% EtOAc/hexanes gradient) to afford tert-butyl 4-(2-fluoro-5-iodo-4-methoxyphenyl)piperidine-1-carboxylate as a colorless glass. The aqueous layer was then re-extracted with EtOAc (3×100 mL) and the combined extracts were dried (MgSO4), filtered, and the solvent was removed under reduced pressure until a precipitate formed. This solid was collected by filtration and dried in a vacuum oven to afford 4-(2-fluoro-5-iodo-4-methoxyphenyl)piperidine as a off-white solid.

Workup

  1. filtrationThe reaction was filtered through Celite
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residue was redissolved in ether (50 mL)
  4. washwashed with H2O (50 mL)
  5. extractionThe aqueous layer was extracted with ether (3×50 mL)
  6. washthe combined extracts were washed with brine (50 mL)
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customThe residue was purified by flash silica gel chromatography (0-10% EtOAc/hexanes gradient)

Sources & evidence

ORD record
ord-0fa6a0a9f0ee4c53af74cbeb987fd6c8
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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