Iodine → 4-(3-Bromo-phenyl)-4-(4-difluoromethoxy-3-methyl-phenyl)-oxazolidin-2-one

HRID 1946915Notes

Reaction equation

HRID 1946915 reaction equation
II.[Br:3][C:4]1[CH:5]=[C:6]([C:10]([C:12]2[CH:17]=[CH:16][C:15]([O:18][CH:19]([F:21])[F:20])=[C:14]([CH3:22])[CH:13]=2)=[CH2:11])[CH:7]=[CH:8][CH:9]=1.C([N:25](CC)CC)C.[C:30]([O:33]CC)(=[O:32])C>C(#N)C.[Ag]N=C=O>[Br:3][C:4]1[CH:5]=[C:6]([C:10]2([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH:19]([F:20])[F:21])=[C:14]([CH3:22])[CH:13]=3)[CH2:11][O:33][C:30](=[O:32])[NH:25]2)[CH:7]=[CH:8][CH:9]=1

Participants

7

Reactant 4

HCID 807IodineHCID 8471TriethylamineHCID 8857Ethyl Acetate2×HCID 578252414-[1-(3-Bromophenyl)vinyl]-1-difluoromethoxy-2-methylbenzene

Product 1

HCID 681534954-(3-Bromo-phenyl)-4-(4-difluoromethoxy-3-methyl-phenyl)-oxazolidin-2-oneYield 67%

Reagents, catalysts & solvents 2

HCID 178521675HCID 178521675, compoundCatalystHCID 6342AcetonitrileSolvent

Procedure

A solution of iodine (5.5 g, 1.1 eq.) in ethyl acetate (60 ml) was added dropwise to a suspension of silver isocyanate (3.3 g, 1.2 eq) and 4-[1-(3-bromo-phenyl)-vinyl]-1-difluoromethoxy-2-methyl-benzene (CAS 1180015-79-9) (6.7 g, 1 eq.) in acetonitrile (80 ml) and ethyl acetate (20 ml). During the addition the suspension was cooled in an ice-bath. The resulting brown suspension was stirred for 1 hour at room temperature. After an TLC sample indicated complete conversion of the starting material, the reaction mixture was filtrated and concentrated in vacuo. The crude was dissolved in tert-butanol (100 ml) and triethylamine (2.76 ml, 1 eq.) was added. The mixture was stirred at 100° C. overnight. For the workup the mixture was allowed to cool to room temperature, then the solvent was removed at reduced pressure and the residue taken up in ethyl acetate. The solution was washed with water (3×20 ml), dried over sodium sulphate and concentrated at reduced pressure. The residue was purified by chromatography on silica gel using a 9:1-mixture of cyclohexane and ethyl acetate as the eluent. There were obtained 5.1 g (67% of theory) of the (RS)-4-(3-bromo-phenyl)-4-(4-difluoromethoxy-3-methyl-phenyl)-oxazolidin-2-one as a white solid. MS (ISP): m/z=398 [M+H]+.

Workup

  1. additionDuring the addition the suspension
  2. temperaturewas cooled in an ice-bath
  3. filtrationthe reaction mixture was filtrated
  4. concentrationconcentrated in vacuo
  5. dissolutionThe crude was dissolved in tert-butanol (100 ml)
  6. stirringThe mixture was stirred at 100° C. overnight
  7. temperatureto cool to room temperature
  8. customthe solvent was removed at reduced pressure
  9. washThe solution was washed with water (3×20 ml)
  10. dry with materialdried over sodium sulphate
  11. concentrationconcentrated at reduced pressure
  12. customThe residue was purified by chromatography on silica gel using a 9

Sources & evidence

ORD record
ord-20f081124e744440b55cdf886038dbf2
Source dataset
uspto-grants-2013_03
Patent number
US08399459B2

Reaction notes

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