Sodium Iodide → Ethyl 3-{3,4-difluoro-5-[(1S)-1-hydroxy-2-iodoethyl]phenyl}propanoate

HRID 602042Notes

Reaction equation

HRID 602042 reaction equation
[I-:1].[Na+].[F:3][C:4]1[CH:5]=[C:6]([CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:7]=[C:8]([C@H:11]([OH:24])[CH2:12]OS(C2C=CC(C)=CC=2)(=O)=O)[C:9]=1[F:10]>CC(C)=O>[F:3][C:4]1[CH:5]=[C:6]([CH2:25][CH2:26][C:27]([O:29][CH2:30][CH3:31])=[O:28])[CH:7]=[C:8]([C@H:11]([OH:24])[CH2:12][I:1])[C:9]=1[F:10]

Participants

4

Reactant 2

HCID 5238Sodium IodideHCID 86638765Ethyl 3-[3,4-difluoro-5-((1S)-1-hydroxy-2-{[(4-methylphenyl)sulfonyl]oxy}ethyl)phenyl]propanoate

Product 1

HCID 68794275Ethyl 3-{3,4-difluoro-5-[(1S)-1-hydroxy-2-iodoethyl]phenyl}propanoateYield 65%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

Sodium iodide (3.34 g, 22.3 mmol) was added to a solution of ethyl 3-[3,4-difluoro-5-((1S)-1-hydroxy-2-{[(4-methylphenyl)sulfonyl]oxy}ethyl)phenyl]propanoate (0.950 g, 2.22 mmol) in acetone (9.0 mL). The reaction mixture was heated at reflux for 18 h. The reaction was cooled to room temperature and concentrated. The residue was diluted with H2O and extracted two times with ethyl acetate. The combined organic layers were washed with H2O and brine, dried over Na2SO4, filtered, and concentrated. Column chromatography (0-40% ethyl acetate:hexane) afforded 0.552 g (65%) of product: 1H NMR (400 MHz, chloroform-d) δ ppm 7.13 (d, J=5.81 Hz, 1 H) 7.01 (dd, J=10.61, 7.58 Hz, 1 H) 5.09 (dd, J=8.34, 3.54 Hz, 1 H) 4.15 (q, J=7.07 Hz, 2 H) 3.58 (dd, J=10.23, 3.16 Hz, 1 H) 3.41 (dd, J=10.36, 8.34 Hz, 1 H) 2.94 (t, J=7.58 Hz, 2 H) 2.62 (t, J=7.71 Hz, 2 H) 2.26 (s, 1 H) 1.26 (t, J=7.20 Hz, 3 H).

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux for 18 h
  3. concentrationconcentrated
  4. additionThe residue was diluted with H2O
  5. extractionextracted two times with ethyl acetate
  6. washThe combined organic layers were washed with H2O and brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-1541552a2fee441ab29ddfa902a5231b
Source dataset
uspto-grants-2011_03
Patent number
US07902394B2

Reaction notes

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