Citric Acid → (R)-2-[[1-(2-iodophenyl)ethoxy]methyl]oxirane

HRID 1181604Notes

Reaction equation

HRID 1181604 reaction equation
[I:1][CH2:2][C:3]([C:5]1[CH:10]=[CH:9]C=CC=1)=O.[BH4-].[Na+].C(O)(=O)C[C:15]([CH2:20][C:21]([OH:23])=O)(C(O)=O)O.[CH2:26]([OH:28])[CH3:27].[CH3:29]O>>[I:1][C:2]1[CH:3]=[CH:5][CH:10]=[CH:9][C:27]=1[CH:26]([O:28][CH2:15][C@H:20]1[CH2:21][O:23]1)[CH3:29]

Participants

6

Reactant 5

HCID 311Citric AcidHCID 702EthanolHCID 887MethanolHCID 138307Ethanone, 2-iodo-1-phenyl-HCID 4311764Sodium borohydride

Product 1

HCID 58662610(R)-2-[[1-(2-iodophenyl)ethoxy]methyl]oxirane

Procedure

2-Iodoacetophenone (6.30 g) was dissolved in methanol (50 ml), sodium borohydride (726 mg) was added and the mixture was stirred at room temperature for 1.5 hr. 10% Aqueous citric acid was added to the reaction mixture and ethanol was evaporated. Water was added and the mixture was extracted 3 times with ethyl acetate. The organic layer was washed successively with saturated aqueous sodium hydrogencarbonate and brine, and dried over sodium sulfate. The organic layer was concentrated under reduced pressure and the obtained residue was dissolved in tetrahydrofuran (50 ml). The solution was cooled to 0° C., sodium hydride (1.54 g, 60% in oil), (R)-glycidyl nosylate (9.95 g) and dimethyl sulfoxide (10 ml) were successively added, and the mixture was stirred overnight at 0° C.—room temperature. 10% Aqueous citric acid was added to neutralize the reaction mixture, and extracted 3 times with ethyl acetate. The organic layer was washed successively with water (twice) and brine, and dried over sodium sulfate. The organic layer was concentrated under reduced pressure and the obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1) to give the title compound (6.36 g).

Workup

  1. customwas evaporated
  2. additionWater was added
  3. extractionthe mixture was extracted 3 times with ethyl acetate
  4. washThe organic layer was washed successively with saturated aqueous sodium hydrogencarbonate and brine
  5. dry with materialdried over sodium sulfate
  6. concentrationThe organic layer was concentrated under reduced pressure
  7. dissolutionthe obtained residue was dissolved in tetrahydrofuran (50 ml)
  8. temperatureThe solution was cooled to 0° C.
  9. additionsodium hydride (1.54 g, 60% in oil), (R)-glycidyl nosylate (9.95 g) and dimethyl sulfoxide (10 ml) were successively added
  10. stirringthe mixture was stirred overnight at 0° C.—room temperature
  11. addition10% Aqueous citric acid was added
  12. extractionextracted 3 times with ethyl acetate
  13. washThe organic layer was washed successively with water (twice) and brine
  14. dry with materialdried over sodium sulfate
  15. concentrationThe organic layer was concentrated under reduced pressure
  16. customthe obtained residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1)

Sources & evidence

ORD record
ord-e3aa3e83544c4822acecb478e1d8bdfa
Source dataset
uspto-grants-2007_10
Patent number
US07285572B2

Reaction notes

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