Acetone → Ethyl 7-(Benzyloxy)chroman-2-carboxylate

HRID 479647Notes

Reaction equation

HRID 479647 reaction equation
CC(C)=O.[OH:5][C:6]1[CH:15]=[C:14]2[C:9]([CH2:10][CH2:11][CH:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[O:13]2)=[CH:8][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].[CH2:27](Br)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1>CCOC(C)=O>[CH2:27]([O:5][C:6]1[CH:15]=[C:14]2[C:9]([CH2:10][CH2:11][CH:12]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[O:13]2)=[CH:8][CH:7]=1)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1

Participants

6

Reactant 4

HCID 180AcetoneHCID 7498Benzyl BromideHCID 11430Potassium CarbonateHCID 11085381Ethyl 7-hydroxychromane-2-carboxylate

Product 1

HCID 11162736Ethyl 7-(Benzyloxy)chroman-2-carboxylateYield 86%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a 5 L acetone solution of ethyl 7-hydroxy-chromane-2-carboxylate (630.1 g, 2.84 mol) was added potassium carbonate powder (785 g, 5.68 mol) and benzyl bromide (405 ml, 3.41 mol). The resulting suspension was heated to reflux for 16 hr. The reaction mixture was filtered through a pad of celite. The filtrate was concentrated to give solid material, which was re-dissolved in AcOEt, washed with water to remove residual salt, dried over MgSO4, filtered, concentrated to a small volume. Addition of hexanes caused precipitation of the title compound, which was collected by suction-filtration. The filtrate was triturated from dichloromethane-hexanes to give more precipitates. Finally the filtrate was concentrated and chromatographed on silica gel eluting with 20 to 80% dichloromethane/hexanes. Combination of all crops yielded the title compound 760.2 g as off-white solid (86%).

Workup

  1. temperatureThe resulting suspension was heated
  2. temperatureto reflux for 16 hr
  3. filtrationThe reaction mixture was filtered through a pad of celite
  4. concentrationThe filtrate was concentrated
  5. customto give solid material, which
  6. washwashed with water
  7. customto remove residual salt
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated to a small volume
  11. additionAddition of hexanes
  12. customprecipitation of the title compound, which
  13. filtrationwas collected by suction-filtration
  14. customThe filtrate was triturated from dichloromethane-hexanes
  15. customto give more
  16. customprecipitates
  17. concentrationFinally the filtrate was concentrated
  18. customchromatographed on silica gel eluting with 20 to 80% dichloromethane/hexanes

Sources & evidence

ORD record
ord-49f774d1389a4909ad645424c99357db
Source dataset
uspto-grants-2003_11
Patent number
US06645997B2

Reaction notes

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