Potassium Carbonate → (2R)-2-[(5-Bromo-2,3-difluorophenoxy)methyl]oxirane

HRID 1948762Notes

Reaction equation

HRID 1948762 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([F:10])[C:5]([F:9])=[C:6]([OH:8])[CH:7]=1.C([O-])([O-])=O.[K+].[K+].[CH2:17]1[O:19][C@H:18]1[CH2:20]OS(C1C=C([N+]([O-])=O)C=CC=1)(=O)=O>CC(C)=O>[Br:1][C:2]1[CH:3]=[C:4]([F:10])[C:5]([F:9])=[C:6]([CH:7]=1)[O:8][CH2:20][C@H:18]1[CH2:17][O:19]1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 146513Benzenesulfonic acid, 3-nitro-, (2R)-2-oxiranylmethyl esterHCID 27733075-Bromo-2,3-Difluorophenol

Product 1

HCID 53470866(2R)-2-[(5-Bromo-2,3-difluorophenoxy)methyl]oxiraneYield 97%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

To an acetone solution (0.1 M, 240 mL) of commercially available 5-bromo-2,3-difluorophenol (5.0 g, 23.93 mmol) was added K2CO3 (9.92 g, 71.77 mmol), and the mixture was heated to reflux for 30 min. After cooling this mixture to RT, (2R)-(−)-glycidyl 3-nitrobenzenesulfonate (6.20 g, 23.93 mmol) was added, and the resulting mixture was heated to reflux overnight. After cooling to RT, the solids were removed by filtration and washed well with ethyl acetate. The filtrate was concentrated and partitioned between ethyl acetate and 1N HCl. The organic portion was washed successively with 5% NaHCO3 and brine, dried (MgSO4), filtered and concentrated to a solid. Purification by FCC (15% ethyl acetate/hexanes) gave the product as a white solid in 97% yield (6.19 g).

Workup

  1. temperaturethe mixture was heated
  2. temperatureto reflux for 30 min
  3. temperaturethe resulting mixture was heated
  4. temperatureto reflux overnight
  5. temperatureAfter cooling to RT
  6. customthe solids were removed by filtration
  7. washwashed well with ethyl acetate
  8. concentrationThe filtrate was concentrated
  9. custompartitioned between ethyl acetate and 1N HCl
  10. washThe organic portion was washed successively with 5% NaHCO3 and brine
  11. dry with materialdried (MgSO4)
  12. filtrationfiltered
  13. concentrationconcentrated to a solid
  14. customPurification by FCC (15% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-4563c74db2dd4cc5bd1e5cb212bbb3b2
Source dataset
uspto-grants-2013_03
Patent number
US08399517B2

Reaction notes

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