Iodine → HCID 57704817, compound

HRID 607047Notes

Reaction equation

HRID 607047 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]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:12][CH2:11]1.[I:22]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:22])=[CH:4][C:3]=1[CH:10]1[CH2:15][CH2:14][N:13]([CH2:16][C:17]([O:19][CH2:20][CH3:21])=[O:18])[CH2:12][CH2:11]1

Participants

5

Reactant 2

HCID 807IodineHCID 86630534HCID 86630534, compound

Product 1

HCID 57704817HCID 57704817, compound

Reagents, catalysts & solvents 2

HCID 178418844HCID 178418844, compoundCatalystHCID 887MethanolSolvent

Procedure

A mixture of ethyl [4-(2-fluoro-4-methoxyphenyl)piperidin-1-yl]acetate (Step A; 21.6 mg; 0.073 mmol), iodine (45.6 mg; 0.146 mmol) and silver sulfate (37 mg; 0.146 mmol) in MeOH (1.5 mL) 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 (25 mL) and washed with H2O (25 mL). The aqueous layer was extracted with ether (3×25 mL) and the combined extracts were washed with brine (25 mL), dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography (0-10% EtOAc/hexanes gradient) to afford ethyl [4-(2-fluoro-5-iodo-4-methoxyphenyl)piperidin-1-yl]acetate as a yellow oil. LCMS=421.8 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.61 (d, J=8.3 Hz, 1H), 6.45 (d, J=11.9 Hz, 1H), 4.21 (q, J=7.1 Hz, 2H), 3.84 (s, 3H), 3.26 (s, 2H), 3.05 (d, J=11.2 Hz, 2H), 2.80 (tt, J=12.0, 3.9 Hz, 1H), 2.33 (t, J=10.6 Hz, 2H), 1.87 (qd, J=12.3, 3.2 Hz, 2H), 1.78 (d, J=12.1 Hz, 2H), 1.29 (t, J=7.1 Hz, 3H).

Workup

  1. filtrationThe reaction was filtered through Celite
  2. concentrationthe filtrate was concentrated in vacuo
  3. dissolutionThe residue was redissolved in ether (25 mL)
  4. washwashed with H2O (25 mL)
  5. extractionThe aqueous layer was extracted with ether (3×25 mL)
  6. washthe combined extracts were washed with brine (25 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-e4ae8541cb04475985be5c39ee043578
Source dataset
uspto-grants-2011_03
Patent number
US07915271B2

Reaction notes

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