HCID 66884069, compound → HCID 66882846, compound

HRID 915366Notes

Reaction equation

HRID 915366 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([C:15](=[O:31])[CH2:16][C:17]2[CH:29]=[CH:28][CH:27]=[C:26]([Cl:30])[C:18]=2[C:19](N(CC)CC)=[O:20])=[CH:11][CH:10]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1>C(O)(=O)CC.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:10]=[CH:11][C:12]([C:15]2[O:31][C:19](=[O:20])[C:18]3[C:17]([CH:16]=2)=[CH:29][CH:28]=[CH:27][C:26]=3[Cl:30])=[CH:13][CH:14]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

4

Reactant 1

HCID 66884069HCID 66884069, compound

Product 1

HCID 66882846HCID 66882846, compoundYield 73%

Reagents, catalysts & solvents 2

HCID 1032Propionic AcidSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
165 °C

Procedure

In a 10 mL round bottomed flask equipped with a magnetic stir bar 2-[2-(4-benzyloxyphenyl)-2-oxo-ethyl]-6-chloro-N,N-diethylbenzamide (340 mg, 0.78 mmol) was treated with propionic acid (1.5 mL). The resulting mixture was stirred and heated to reflux in a 165° C. oil bath. As the reaction heated, the 2-[2-(4-benzyloxyphenyl)-2-oxo-thyl]-6-chloro-N,N-diethylbenzamide was dissolved in the propionic acid to afford a pale brown solution. After stirring at reflux for 88 hours, the reaction was analyzed by TLC, which showed no starting material remaining. The reaction was allowed to cool to ambient temperature during which time a mass of pale brown crystals were deposited on the walls of the reaction flask. The reaction mixture was diluted with ethyl acetate to dissolve the solids, and the resulting solution was washed with saturated aqueous NaHCO3 solution. The basic aqueous solution was then extracted with EtOAc (3×20 mL). The combined organic extracts were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure to afford an off-white solid. This material was quite clean by 1H NMR analysis and was further purified by recrystallization from EtOAc to afford 3-(4-benzyloxyphenyl)-8-chloro-isochromen-1-one (206 mg, 73% yield) as pale yellow crystals.

Workup

  1. temperatureheated
  2. temperatureAs the reaction heated
  3. customto afford a pale brown solution
  4. stirringAfter stirring
  5. temperatureat reflux for 88 hours
  6. temperatureto cool to ambient temperature during which time a mass of pale brown crystals
  7. dissolutionto dissolve the solids
  8. washthe resulting solution was washed with saturated aqueous NaHCO3 solution
  9. extractionThe basic aqueous solution was then extracted with EtOAc (3×20 mL)
  10. washThe combined organic extracts were washed with brine
  11. dry with materialdried over Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated under reduced pressure
  14. customto afford an off-white solid
  15. customwas further purified by recrystallization from EtOAc

Sources & evidence

ORD record
ord-7f54a65781e044288bdc651414aa1f8e
Source dataset
uspto-grants-2007_09
Patent number
US07265131B2

Reaction notes

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