Tetrahydrofuran → 3-(2-chloro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-phenyl)-4H-[1,2,4]oxadiazol-5-one

HRID 1172684Notes

Reaction equation

HRID 1172684 reaction equation
Cl[C:2]1[CH:9]=[C:8]([O:10][CH:11]([C:13]2[S:17][C:16]([C:18]3[CH:23]=[CH:22][C:21]([C:24]([F:27])([F:26])[F:25])=[CH:20][CH:19]=3)=[N:15][C:14]=2[CH3:28])[CH3:12])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[ClH:29].[NH2:30][OH:31].C(N(CC)CC)C.[O:39]1CCC[CH2:40]1>CO>[Cl:29][C:2]1[CH:9]=[C:8]([O:10][CH:11]([C:13]2[S:17][C:16]([C:18]3[CH:19]=[CH:20][C:21]([C:24]([F:26])([F:25])[F:27])=[CH:22][CH:23]=3)=[N:15][C:14]=2[CH3:28])[CH3:12])[CH:7]=[CH:6][C:3]=1[C:4]1[NH:5][C:40](=[O:39])[O:31][N:30]=1

Participants

6

Reactant 4

HCID 8028TetrahydrofuranHCID 8471TriethylamineHCID 443297Hydroxyamine hydrochlorideHCID 595563342-Chloro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-benzonitrile

Product 1

HCID 1355241613-(2-chloro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-phenyl)-4H-[1,2,4]oxadiazol-5-one

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Conditions

Temperature
60 °C

Procedure

2.1 g 2-Chloro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-benzonitrile were dissolved in a mixture of 20 ml tetrahydrofuran and 20 ml methanol. 3.29 g hydroxylamine hydrochloride were added followed by the addition of 5.74 ml triethylamine. The reaction mixture was stirred at 60° C. overnight. The solvents were removed in vacuo and the resulting residue poured into water and extracted five times with ethyl acetate. The combined organic extracts were washed with brine, dried over MgSO4 and the solvent was evaporated in vacuo. The residue was dissolved in 10 ml dichloromethane. 0.50 ml pyridine and 0.77 ml phenylchloroformate were added and the mixture stirred at room temperature for fifteen minutes. The mixture was diluted by the addition of 25 ml acetonitrile and 3.54 ml 1,8-diazabicyclo[5.4.0]undec-7-ene were added. The mixture was stirred at room temperature for thirty minutes. The mixture was evaporated in vacuo and the resulting crude material was purified by RP-HPLC to obtain 0.50 g 3-(2-chloro-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-ethoxy}-phenyl)-4H-[1,2,4]oxadiazol-5-one.

Workup

  1. customThe solvents were removed in vacuo
  2. additionthe resulting residue poured into water
  3. extractionextracted five times with ethyl acetate
  4. washThe combined organic extracts were washed with brine
  5. dry with materialdried over MgSO4
  6. customthe solvent was evaporated in vacuo
  7. dissolutionThe residue was dissolved in 10 ml dichloromethane
  8. addition0.50 ml pyridine and 0.77 ml phenylchloroformate were added
  9. stirringthe mixture stirred at room temperature for fifteen minutes
  10. additionThe mixture was diluted by the addition of 25 ml acetonitrile and 3.54 ml 1,8-diazabicyclo[5.4.0]undec-7-ene
  11. additionwere added
  12. stirringThe mixture was stirred at room temperature for thirty minutes
  13. customThe mixture was evaporated in vacuo
  14. customthe resulting crude material was purified by RP-HPLC

Sources & evidence

ORD record
ord-89dad4271a6246ae841c50e8a5bb84c3
Source dataset
uspto-grants-2010_11
Patent number
US07834030B2

Reaction notes

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