Ethylene Glycol → 2-[4-Iodo-2-(trifluoromethyl)phenyl]-1,3-dioxolane

HRID 70323Notes

Reaction equation

HRID 70323 reaction equation
[I:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#N)=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=1.CC(C[AlH]CC(C)C)C.CC1C=CC(S(O)(=O)=O)=CC=1.O.[CH2:35]([OH:38])[CH2:36][OH:37]>C(Cl)Cl.C1C=CC=CC=1>[I:1][C:2]1[CH:9]=[CH:8][C:5]([CH:6]2[O:38][CH2:35][CH2:36][O:37]2)=[C:4]([C:10]([F:13])([F:12])[F:11])[CH:3]=1

Participants

7

Reactant 4

HCID 174Ethylene GlycolHCID 14487Diisobutylaluminum hydrideHCID 521998p-Toluenesulfonic acid monohydrateHCID 162183374-Iodo-2-(trifluoromethyl)benzonitrile

Product 1

HCID 582766812-[4-Iodo-2-(trifluoromethyl)phenyl]-1,3-dioxolane

Reagents, catalysts & solvents 2

HCID 241BenzeneSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 4-iodo-2-(trifluoromethyl)benzonitrile (1.89 g; 6.38 mmol, Note 1) in CH2Cl2 (15 mL) at −40° C. was added DIBAL-H (9.6 mL of a 1.0M solution in CH2Cl2; 9.6 mmol), dropwise over 5 min. The mixture was stirred 30 min, quenched by dropwise addition of MeOH and removed from the cooling bath. To the still-cold mixture was slowly added HCl (10 mL of a 6M solution), and after stirring 30 min at room temperature the layers were separated. The aqueous layer was extracted with CH2Cl2 (×2), combined organics were washed (water, brine), dried over Na2SO4 and concentrated in vacuo. The residue was dissolved in PhH (15 mL), along with TsOH.H2O (0.12 g; 0.64 mmol) and ethylene glycol (3.5 mL; 63 mmol), and the solution was heated under reflux for 2 h using a Dean-Stark trap to remove water. Upon cooling, the mixture was diluted with <solvent>, washed (water, brine), dried over Na2SO4, and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a pale yellow oil. 1H NMR (400 MHz, CDCl3) δ ppm 4.00-4.11 (m, 2 H), 4.11-4.24 (m, 2 H), 6.06 (s, 1 H), 7.54 (d, J=8.4 Hz, 1 H), 7.93 (d, J=8.4 Hz, 1 H), 7.99 (s, 1 H).

Workup

  1. customquenched by dropwise addition of MeOH
  2. customremoved from the cooling bath
  3. stirringafter stirring 30 min at room temperature the layers
  4. customwere separated
  5. extractionThe aqueous layer was extracted with CH2Cl2 (×2)
  6. washcombined organics were washed (water, brine)
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated in vacuo
  9. temperaturethe solution was heated
  10. temperatureunder reflux for 2 h
  11. customto remove water
  12. temperatureUpon cooling
  13. additionthe mixture was diluted with <solvent>
  14. washwashed (water, brine)
  15. dry with materialdried over Na2SO4
  16. concentrationconcentrated in vacuo
  17. customThe residue was purified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-d8911cbbd70944899fe4ee5caf60b0ba
Source dataset
uspto-grants-2014_09
Patent number
US08822518B2

Reaction notes

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