Ethylene Glycol → 1-(5-Chloro-2-ethoxy-3-iodo-4-methylphenyl)ethanol

HRID 1499951Notes

Reaction equation

HRID 1499951 reaction equation
[Cl:1][C:2]1[C:3](F)=[C:4]([I:14])[C:5]([O:11][CH2:12][CH3:13])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.[CH2:16](O)CO>C1(C)C=CC=CC=1.O.C1(C)C=CC(S(O)(=O)=O)=CC=1>[Cl:1][C:2]1[C:3]([CH3:16])=[C:4]([I:14])[C:5]([O:11][CH2:12][CH3:13])=[C:6]([CH:8]([OH:10])[CH3:9])[CH:7]=1

Participants

5

Reactant 2

HCID 174Ethylene GlycolHCID 866669601-(5-Chloro-2-ethoxy-4-fluoro-3-iodophenyl)ethanone

Product 1

HCID 866778481-(5-Chloro-2-ethoxy-3-iodo-4-methylphenyl)ethanolYield 110.6%

Reagents, catalysts & solvents 2

HCID 521998p-Toluenesulfonic acid monohydrateCatalystHCID 1140TolueneSolvent

Procedure

A solution of 1-(5-chloro-2-ethoxy-4-fluoro-3-iodophenyl)ethanone (20.0 g, 58.4 mmol; Example 212, step 1) and 1,2-ethanediol (6.5 mL, 120 mmol) in toluene (190 mL) was treated with p-toluenesulfonic acid monohydrate (1.1 g, 5.8 mmol). The flask was fitted with a Dean-Stark trap that was filled with sieves, and refluxed for 3 h. The reaction mixture was cooled and added to ice cooled saturated sodium bicarbonate solution (250 mL) and extracted with ethyl acetate. The organic layer was washed with brine, dried over sodium sulfate, filtered, and concentrated to a crude orange oil. The crude material was purified by flash column chromatography using ethyl acetate in hexanes (0%-20%) to give the desired product (22 g, 99%). LCMS for C12H14ClFIO3 (M+H)+: m/z=387.0; Found: 386.9.

Workup

  1. customThe flask was fitted with a Dean-Stark trap that
  2. additionwas filled with sieves
  3. temperaturerefluxed for 3 h
  4. temperatureThe reaction mixture was cooled
  5. extractionextracted with ethyl acetate
  6. washThe organic layer was washed with brine
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated to a crude orange oil
  10. customThe crude material was purified by flash column chromatography

Sources & evidence

ORD record
ord-e77ee8b382294222a37520eae6ce59ce
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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