Hydrochloric Acid → (αZ)-4-Bromo-α-[[[4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]phenyl]methoxy]imino]benzeneacetic acid

HRID 584411Notes

Reaction equation

HRID 584411 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:9]=[CH:8][C:7](/[C:10](=[N:16]/[OH:17])/[C:11]([O:13]CC)=[O:12])=[CH:6][CH:5]=1.Cl[CH2:19][C:20]1[CH:39]=[CH:38][C:23]([O:24][CH2:25][C:26]2[N:27]=[C:28]([C:32]3[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=3)[O:29][C:30]=2[CH3:31])=[CH:22][CH:21]=1.Cl.C(=O)(O)[O-].[Na+]>CN(C)C=O>[Br:3][C:4]1[CH:5]=[CH:6][C:7](/[C:10](=[N:16]/[O:17][CH2:19][C:20]2[CH:21]=[CH:22][C:23]([O:24][CH2:25][C:26]3[N:27]=[C:28]([C:32]4[CH:37]=[CH:36][CH:35]=[CH:34][CH:33]=4)[O:29][C:30]=3[CH3:31])=[CH:38][CH:39]=2)/[C:11]([OH:13])=[O:12])=[CH:8][CH:9]=1

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 516892Sodium BicarbonateHCID 109469404-(4-Chloromethylphenoxy)methyl-5-methyl-2-phenyloxazoleHCID 11086886HCID 11086886, compound

Product 1

HCID 11049621(αZ)-4-Bromo-α-[[[4-[(5-methyl-2-phenyl-4-oxazolyl)methoxy]phenyl]methoxy]imino]benzeneacetic acidYield 81%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% in oil, 127 mg) was added under a nitrogen atmosphere to a solution of ethyl Z-2-(4-bromophenyl)-2-hydroxyiminoacetate (868 mg) and 4-(4-chloromethylphenoxymethyl)-5-methyl-2-phenyloxazole (100 g) in N,N-dimethylformamide (10 ml) at room temperature and the mixture was stirred for 1 hour. After adding 1N HCl (5 ml), aqueous sodium bicarbonate was added, and then the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride, dried (MgSO4) and then concentrated. The residue was subjected to column chromatography on silica gel to obtain an oil from a fraction eluted with ethyl acetate-hexane (1:2, v/v). This oil was dissolved in tetrahydrofuran (5 ml)-methanol (10 ml), and 0.5N aqueous solution of sodium hydroxide (10 ml) was added and the mixture was heated under reflux for 1.5 hours. 1N HCl (5.5 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride, dried (MgSO4) and then concentrated. The residual crystal was recrystallized from ethyl acetate to obtain Z-2-(4-bromophenyl)-2-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyloxyimino]acetic acid (1.34 g, yield 81%) as colorless crystals. m.p. 189-190° C. (decomposition)

Workup

  1. additionwas added
  2. extractionthe mixture was extracted with ethyl acetate
  3. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated
  6. customto obtain an oil from a fraction
  7. washeluted with ethyl acetate-hexane (1:2
  8. dissolutionThis oil was dissolved in tetrahydrofuran (5 ml)-methanol (10 ml), and 0.5N aqueous solution of sodium hydroxide (10 ml)
  9. additionwas added
  10. temperaturethe mixture was heated
  11. temperatureunder reflux for 1.5 hours
  12. addition1N HCl (5.5 ml) was added to the reaction mixture
  13. extractionthe mixture was extracted with ethyl acetate
  14. washThe ethyl acetate layer was washed with saturated aqueous sodium chloride
  15. dry with materialdried (MgSO4)
  16. concentrationconcentrated
  17. customThe residual crystal was recrystallized from ethyl acetate

Sources & evidence

ORD record
ord-410d9dceb12f4c37a4ec871b932ad5f0
Source dataset
uspto-grants-2005_08
Patent number
US06924300B2

Reaction notes

Loading…