Triethylamine → 6-bromo-2,2-dimethyl-4-methylene-4H-spiro[chromene-3,3'-oxetane]

HRID 873742Notes

Reaction equation

HRID 873742 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][C:7]([CH3:13])([CH3:12])[C:6]([CH2:16][OH:17])([CH2:14]O)[C:5]2=[CH2:18].CS(Cl)(=O)=O.CCN(CC)CC.[OH-].[Na+]>C1COCC1.O.CCO>[Br:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][C:7]([CH3:13])([CH3:12])[C:6]1([CH2:16][O:17][CH2:14]1)[C:5]2=[CH2:18]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 31297Methanesulfonyl chlorideHCID 867242906-Bromo-2,2-dimethyl-4-methylene-2h-1-benzopyran-3,3(4h)-dimethanol

Product 1

HCID 867242426-bromo-2,2-dimethyl-4-methylene-4H-spiro[chromene-3,3'-oxetane]Yield 26.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Under nitrogen, to a solution of (6-bromo-2,2-dimethyl-4-methylene-3,4-dihydro-2H-chromene-3,3-diyl)dimethanol (800 g, 2.55 mol) and MsCl (877.9 g, 7.66 mol) in THF (4.0 L) was added Et3N (851 g, 8.41 mol) over 45 minutes maintaining the temperature below 0-10° C. The reaction mixture was allowed to warm to room temperature and stirred for 1 hour. EtOH (8 L) and NaOH (1021.8 g, 25.55 mol) were added and the reaction mixture was heated under reflux for 16 hours. Water (4 L) was added and a clear solution was obtained. Most of the solvent was removed under reduced pressure and the resulting residue was extracted with ethyl acetate (1.5 L×2). The combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was dissolved in MeOH (640 mL) at 60° C. and the resulting solution was allowed to cool to room temperature. The precipitation formed was filtered-off. The filtrate was concentrated under reduced pressure and the residue was re-dissolved in MeOH (500 mL) at 60° C. The resulting solution was allowed to cool to room temperature and then further to 0-5° C. The mixture was stirred at 0-5° C. overnight and the precipitated yellow solid was collected by filtration to give 6-bromo-2,2-dimethyl-4-methylene-4H-spiro[chromene-3,3′-oxetane] (197.2 g). The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography on silica gel (petroleum ether/ethyl acetate=50:1) to give another batch of 6-bromo-2,2-dimethyl-4-methylene-4H-spiro[chromene-3,3′-oxetane] (143.6 g).

Workup

  1. temperaturemaintaining the temperature below 0-10° C
  2. temperaturethe reaction mixture was heated
  3. temperatureunder reflux for 16 hours
  4. customa clear solution was obtained
  5. customMost of the solvent was removed under reduced pressure
  6. extractionthe resulting residue was extracted with ethyl acetate (1.5 L×2)
  7. washThe combined extracts were washed with brine
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. dissolutionThe residue was dissolved in MeOH (640 mL) at 60° C.
  11. temperatureto cool to room temperature
  12. customThe precipitation
  13. customformed
  14. concentrationThe filtrate was concentrated under reduced pressure
  15. dissolutionthe residue was re-dissolved in MeOH (500 mL) at 60° C
  16. temperatureto cool to room temperature
  17. customfurther to 0-5° C
  18. stirringThe mixture was stirred at 0-5° C. overnight
  19. filtrationthe precipitated yellow solid was collected by filtration

Sources & evidence

ORD record
ord-e8a8e5833276408388be004d12efd3ce
Source dataset
uspto-grants-2015_03
Patent number
US08975415B2

Reaction notes

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