Water → 3-(2-difluoromethoxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-phenyl)-4H-1,2,4-oxadiazol-5-one

HRID 1172694Notes

Reaction equation

HRID 1172694 reaction equation
[F:1][CH:2]([F:34])[O:3][C:4]1[CH:13]=[C:12]([O:14][CH:15]([C:18]2[S:22][C:21]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[N:20][C:19]=2[CH3:33])[CH2:16][CH3:17])[CH:11]=[CH:10][C:5]=1[C:6]([NH:8][OH:9])=[NH:7].C(N(CC)C(C)C)(C)C.Cl[C:45](OC1C=CC=CC=1)=[O:46].O>O1CCCC1>[F:34][CH:2]([F:1])[O:3][C:4]1[CH:13]=[C:12]([O:14][CH:15]([C:18]2[S:22][C:21]([C:23]3[CH:28]=[CH:27][C:26]([C:29]([F:32])([F:31])[F:30])=[CH:25][CH:24]=3)=[N:20][C:19]=2[CH3:33])[CH2:16][CH3:17])[CH:11]=[CH:10][C:5]=1[C:6]1[NH:7][C:45](=[O:46])[O:9][N:8]=1

Participants

6

Reactant 4

HCID 962WaterHCID 15891Phenyl chloroformateHCID 81531DiisopropylethylamineHCID 178458446HCID 178458446, compound

Product 1

HCID 1360146463-(2-difluoromethoxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-phenyl)-4H-1,2,4-oxadiazol-5-one

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 315 mg of 2-difluoromethoxy-N-hydroxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-benzamidine in 6.5 mL of tetrahydrofuran at 0° C. was added 1.5 mL of N,N-diisopropylethylamine followed by 0.08 mL of phenyl chloroformate. The resulting mixture was stirred for 5 minutes at 0° C. then poured into water and extracted with dichloromethane. The organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The residue was dissolved 6.5 mL of tetrahydrofuran and 0.3 mL of N,N-diisopropylethylamine. The resulting solution was heated in a sealed tube to 150° C. under microwave irradiation for 15 minutes. After allowing it to cool down to room temperature, the mixture was poured into water and extracted with dichloromethane. The organic extracts were dried over magnesium sulfate, filtered and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel (diisopropyl ether 100 followed by a gradient from dichloromethane 100 to dichloromethane 90/methanol 10) to give 31 mg of 3-(2-difluoromethoxy-4-{1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-phenyl)-4H-1,2,4-oxadiazol-5-one.

Workup

  1. extractionextracted with dichloromethane
  2. dry with materialThe organic extracts were dried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. dissolutionThe residue was dissolved 6.5 mL of tetrahydrofuran and 0.3 mL of N,N-diisopropylethylamine
  6. temperatureThe resulting solution was heated in a sealed tube to 150° C. under microwave irradiation for 15 minutes
  7. temperatureto cool down to room temperature
  8. additionthe mixture was poured into water
  9. extractionextracted with dichloromethane
  10. dry with materialThe organic extracts were dried over magnesium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated under reduced pressure
  13. customThe crude product was purified by column chromatography on silica gel (diisopropyl ether 100

Sources & evidence

ORD record
ord-49531d775ace4c22a0ebf05f874ed973
Source dataset
uspto-grants-2010_11
Patent number
US07834030B2

Reaction notes

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