Acetonitrile → HCID 58243473, compound

HRID 389145Notes

Reaction equation

HRID 389145 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][C:18]([CH3:36])([C:20]2[N:24]([CH3:25])[C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]([F:35])([F:34])[F:33])=[N:22][N:21]=2)[CH3:19])=[C:6]([C:8]2[O:9][CH:10]=[C:11]([C:13]([O:15]C)=[O:14])[N:12]=2)[CH:7]=1.[Cl:37]N1C(=O)CCC1=O.C(#N)C.[OH-].[Na+]>CO.[Cl-].[Na+].O.O>[Cl:37][C:10]1[O:9][C:8]([C:6]2[CH:7]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=2[O:17][C:18]([CH3:19])([C:20]2[N:24]([CH3:25])[C:23]([C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=3[C:32]([F:33])([F:34])[F:35])=[N:22][N:21]=2)[CH3:36])=[N:12][C:11]=1[C:13]([OH:15])=[O:14]

Participants

8

Reactant 4

HCID 6342AcetonitrileHCID 14798Sodium HydroxideHCID 31398ChlorosuccinimideHCID 58243993HCID 58243993, compound

Product 1

HCID 58243473HCID 58243473, compoundYield 7.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 57417360Sodium chloride; waterSolvent

Procedure

Methyl 2-[5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)phenyl]-1,3-oxazole-4-carboxylate (100 mg) and N-chlorosuccinimide (150 mg) were mixed with acetonitrile (4 ml), followed by heating to reflux for 48 hours. The reaction solution was cooled to room temperature and water was added thereto, followed by extraction with ethyl acetate. The organic layer was washed with water, saturated aqueous sodium bicarbonate solution and then saturated brine in this order, and dried over anhydrous magnesium sulfate. The resulting product was filtered and the solvent was evaporated under reduced pressure. The residue was purified by silica gel chromatography (n-hexane:ethyl acetate=2:1 to 1:10). The resulting residue was dissolved in ethyl acetate, 4M hydrogen chloride-ethyl acetate (1 ml) was added thereto and the solvent was evaporated under reduced pressure. The resulting solid was washed with ethyl acetate to obtain a white solid. The resulting solid was dissolved in methanol (3 ml) and a 1M aqueous sodium hydroxide solution (1 ml) was added thereto, followed by stirring for 30 minutes. Water and saturated brine were added to the reaction solution, followed by washing with ethyl acetate. 1M hydrochloric acid was added to the aqueous layer, followed by extraction with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The resulting solid was washed with ethyl acetate to obtain, as a white solid, 5-chloro-2-[5-chloro-2-(1-methyl-1-{4-methyl-5-[2-(trifluoromethyl)phenyl]-4H-1,2,4-triazol-3-yl}ethoxy)phenyl]-1,3-oxazole-4-carboxylic acid (8.2 mg).

Workup

  1. temperatureby heating
  2. temperatureto reflux for 48 hours
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with water, saturated aqueous sodium bicarbonate solution
  5. dry with materialsaturated brine in this order, and dried over anhydrous magnesium sulfate
  6. filtrationThe resulting product was filtered
  7. customthe solvent was evaporated under reduced pressure
  8. customThe residue was purified by silica gel chromatography (n-hexane:ethyl acetate=2:1 to 1:10)
  9. dissolutionThe resulting residue was dissolved in ethyl acetate
  10. addition4M hydrogen chloride-ethyl acetate (1 ml) was added
  11. customthe solvent was evaporated under reduced pressure
  12. washThe resulting solid was washed with ethyl acetate
  13. customto obtain a white solid
  14. washby washing with ethyl acetate
  15. addition1M hydrochloric acid was added to the aqueous layer
  16. extractionfollowed by extraction with ethyl acetate
  17. washThe organic layer was washed with saturated brine
  18. dry with materialdried over anhydrous magnesium sulfate
  19. customthe solvent was evaporated under reduced pressure
  20. washThe resulting solid was washed with ethyl acetate

Sources & evidence

ORD record
ord-a20ed0920c55413ab82f271a19595709
Source dataset
uspto-grants-2013_02
Patent number
US08377923B2

Reaction notes

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