Ethylene Glycol → Ethyl 2-[4-chloro-3-fluoro-2-iodo-6-(2-methyl-1,3-dioxolan-2-yl)phenoxy]propanoate

HRID 626857Notes

Reaction equation

HRID 626857 reaction equation
[C:1]([C:4]1[C:9]([O:10][CH:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:8]([I:18])[C:7]([F:19])=[C:6]([Cl:20])[CH:5]=1)(=[O:3])[CH3:2].[CH2:21](O)[CH2:22][OH:23].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1>[Cl:20][C:6]1[CH:5]=[C:4]([C:1]2([CH3:2])[O:23][CH2:22][CH2:21][O:3]2)[C:9]([O:10][CH:11]([CH3:17])[C:12]([O:14][CH2:15][CH3:16])=[O:13])=[C:8]([I:18])[C:7]=1[F:19]

Participants

6

Reactant 4

HCID 174Ethylene GlycolHCID 516892Sodium BicarbonateHCID 521998p-Toluenesulfonic acid monohydrateHCID 86697548Ethyl 2-(6-acetyl-4-chloro-3-fluoro-2-iodophenoxy)propanoate

Product 1

HCID 86697549Ethyl 2-[4-chloro-3-fluoro-2-iodo-6-(2-methyl-1,3-dioxolan-2-yl)phenoxy]propanoateYield 57%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of ethyl 2-(6-acetyl-4-chloro-3-fluoro-2-iodophenoxy)propanoate (3.58 g, 8.63 mmol) and 1,2-ethanediol (1.20 mL, 21.6 mmol) in toluene (16.3 mL) was treated with p-toluenesulfonic acid monohydrate (246 mg, 1.30 mmol) and heated at reflux in a flask fitted with a Dean-Stark trap filled with sieves. The reaction mixture was cooled and poured into saturated sodium bicarbonate (150 mL) and extracted with ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated to give a crude residue. Purification by flash column chromatography (100% hexanes to 10% EtOAc/hexanes) gave the desired product (2.25 g, 57%) as a mixture of enantiomers. LCMS calculated for C15H18ClFIO5 (M+H)+: m/z=459.0; found: 459.0.

Workup

  1. temperatureheated
  2. temperatureat reflux in a flask
  3. customfitted with a Dean-Stark trap
  4. additionfilled with sieves
  5. temperatureThe reaction mixture was cooled
  6. extractionextracted with ethyl acetate (2×200 mL)
  7. washThe combined organic layers were washed with brine
  8. dry with materialdried over sodium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customto give a crude residue
  12. customPurification by flash column chromatography (100% hexanes to 10% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d86a311f32f0493797ae752b9bf6a2a0
Source dataset
uspto-grants-2016_04
Patent number
US09309251B2

Reaction notes

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