Hydrochloric Acid → 6-Bromo-2,2-dimethyl-4-methylene-2h-1-benzopyran-3,3(4h)-dimethanol

HRID 873741Notes

Reaction equation

HRID 873741 reaction equation
[CH3:1][Mg+].[Br-].[Br:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[O:11][C:10]([CH3:16])([CH3:15])[C:9]([CH2:19][OH:20])([CH2:17][OH:18])[C:8]2=O.Cl>C1COCC1>[Br:4][C:5]1[CH:6]=[C:7]2[C:12](=[CH:13][CH:14]=1)[O:11][C:10]([CH3:16])([CH3:15])[C:9]([CH2:19][OH:20])([CH2:17][OH:18])[C:8]2=[CH2:1]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 867242446-bromo-3,3-bis(hydroxymethyl)-2,2-dimethyl-2,3-dihydro-4H-chromen-4-oneHCID 178418689HCID 178418689, compound2×

Product 1

HCID 867242906-Bromo-2,2-dimethyl-4-methylene-2h-1-benzopyran-3,3(4h)-dimethanolYield 71.9%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Under nitrogen, MeMgBr solution (2.9 M in 2-methyltetrahydrofuran solution, 3.06 L, 8.88 mol) was diluted by adding into THF (8 L) at 0-5° C. A solution of 6-bromo-3,3-bis(hydroxymethyl)-2,2-dimethyl-2,3-dihydro-4H-chromen-4-one (700 g, 2.22 mol) in THF (5 L) was added dropwise via a dropping funnel to the diluted MeMgBr solution maintaining the temperature below 5° C. After the addition was complete, the reaction mixture was allowed to warm to room temperature and stirred for 30 minutes. Then the reaction mixture was heated under reflux overnight. The mixture was cooled to room temperature followed by cooling with an ice-water bath and 6 M hydrochloric acid (3.7 L, 22.2 mol) was added dropwise via a dropping funnel over 30 minutes maintaining the temperature below 10° C. After the addition was complete, the mixture was allowed to warm to room temperature and stirred for 20 minutes. The mixture was extracted with toluene (5 L×2) and the combined extracts were washed with brine, dried over Na2SO4 and concentrated under reduced pressure. The residue was treated with a mixture of hexane/toluene (5:1, 2 L) and the resulting suspension was stirred for 30 minutes. The precipitate was collected by filtration, washed with hexane and dried under vacuum to give (6-bromo-2,2-dimethyl-4-methylene-3,4-dihydro-2H-chromene-3,3-diyl)dimethanol (500 g).

Workup

  1. temperaturemaintaining the temperature below 5° C
  2. additionAfter the addition
  3. temperatureThen the reaction mixture was heated
  4. temperatureunder reflux overnight
  5. temperatureThe mixture was cooled to room temperature
  6. temperatureby cooling with an ice-water bath
  7. temperaturemaintaining the temperature below 10° C
  8. additionAfter the addition
  9. temperatureto warm to room temperature
  10. stirringstirred for 20 minutes
  11. extractionThe mixture was extracted with toluene (5 L×2)
  12. washthe combined extracts were washed with brine
  13. dry with materialdried over Na2SO4
  14. concentrationconcentrated under reduced pressure
  15. additionThe residue was treated with a mixture of hexane/toluene (5:1, 2 L)
  16. stirringthe resulting suspension was stirred for 30 minutes
  17. filtrationThe precipitate was collected by filtration
  18. washwashed with hexane
  19. customdried under vacuum

Sources & evidence

ORD record
ord-770f8ed03f1f41d9ae5ed8aa6985d6ae
Source dataset
uspto-grants-2015_03
Patent number
US08975415B2

Reaction notes

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