Acetoxyacetyl chloride → 2-[4-(2-Fluoro-5-iodo-4-methoxyphenyl)piperidin-1-yl]-2-oxoethyl acetate

HRID 2093219Notes

Reaction equation

HRID 2093219 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([O:8][CH3:9])[C:5]([I:10])=[CH:4][C:3]=1[CH:11]1[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]1.C(N(CC)C(C)C)(C)C.[C:26]([O:29][CH2:30][C:31](Cl)=[O:32])(=[O:28])[CH3:27]>CN(C=O)C>[C:26]([O:29][CH2:30][C:31]([N:14]1[CH2:13][CH2:12][CH:11]([C:3]2[CH:4]=[C:5]([I:10])[C:6]([O:8][CH3:9])=[CH:7][C:2]=2[F:1])[CH2:16][CH2:15]1)=[O:32])(=[O:28])[CH3:27]

Participants

5

Reactant 3

HCID 26297Acetoxyacetyl chlorideHCID 81531DiisopropylethylamineHCID 577048374-(2-Fluoro-5-iodo-4-methoxyphenyl)piperidine

Product 1

HCID 670659912-[4-(2-Fluoro-5-iodo-4-methoxyphenyl)piperidin-1-yl]-2-oxoethyl acetate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A stirred solution of 4-(2-fluoro-5-iodo-4-methoxyphenyl)piperidine (50 mg; 0.149 mmol) in DMF (1.2 mL) under N2 was treated with N,N-diisopropylethylamine (26 μL; 0.149 mmol), followed by acetoxyacetyl chloride (16 μL, 0.149 mmol). The resultant solution was stirred at room temperature for 5 h. The reaction was partitioned between EtOAc (25 mL) and saturated NaHCO3 (25 mL). The aqueous layer was extracted with EtOAc (3×25 mL) and the combined organic fractions were washed with water and brine (25 mL each), dried (Na2SO4), filtered and concentrated in vacuo. The residue was purified by flash silica gel chromatography, eluting with EtOAC/hexanes, to afford 2-[4-(2-fluoro-5-iodo-4-methoxyphenyl)piperidin-1-yl]-2-oxoethyl acetate as a colorless oil. LCMS=435.8 (M+1)+. 1H NMR (CDCl3, 500 MHz) δ 7.52 (d, J=8.2 Hz, 1 H), 6.56 (d, J=12.2 Hz, 1 H), 4.76 (s, 2 H), 4.76-4.70 (m, 1H), 3.85 (s, 3 H), 3.76 (br d, J=13 Hz, 1 H), 3.17 (t, J=12.6 Hz, 1 H), 2.98 (tt, J=12.1, 3.4 Hz, 1 H), 2.68 (t, J=12.4 Hz, 1 H), 2.20 (s, 3 H), 1.90-1.82 (m, 2 H), 1.70-1.62 (m, 2H).

Workup

  1. customThe reaction was partitioned between EtOAc (25 mL) and saturated NaHCO3 (25 mL)
  2. extractionThe aqueous layer was extracted with EtOAc (3×25 mL)
  3. washthe combined organic fractions were washed with water and brine (25 mL each)
  4. dry with materialdried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash silica gel chromatography
  8. washeluting with EtOAC/hexanes

Sources & evidence

ORD record
ord-c759011ec6e6410dabdca64ac2559cf1
Source dataset
uspto-grants-2013_05
Patent number
US08440702B2

Reaction notes

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