4-Fluoro-3-(trifluoromethyl)benzoyl Chloride → 4-Fluoro-N-{5-[4-(pyridin-3-yloxy)phenyl]-1,3,4-oxadiazol-2-yl}-3-(trifluoromethyl)-benzamide

HRID 387482

Reaction equation

HRID 387482 reaction equation
Br.[N:2]1[CH:7]=[CH:6][CH:5]=[C:4]([O:8][C:9]2[CH:14]=[CH:13][C:12]([C:15]3[O:19][C:18]([NH2:20])=[N:17][N:16]=3)=[CH:11][CH:10]=2)[CH:3]=1.[F:21][C:22]1[CH:30]=[CH:29][C:25]([C:26](Cl)=[O:27])=[CH:24][C:23]=1[C:31]([F:34])([F:33])[F:32]>N1C=CC=CC=1.CO>[F:21][C:22]1[CH:30]=[CH:29][C:25]([C:26]([NH:20][C:18]2[O:19][C:15]([C:12]3[CH:11]=[CH:10][C:9]([O:8][C:4]4[CH:3]=[N:2][CH:7]=[CH:6][CH:5]=4)=[CH:14][CH:13]=3)=[N:16][N:17]=2)=[O:27])=[CH:24][C:23]=1[C:31]([F:32])([F:33])[F:34]

Participants

5

Reactant 2

HCID 1442534-Fluoro-3-(trifluoromethyl)benzoyl ChlorideHCID 686796585-[4-(Pyridin-3-yloxy)phenyl]-1,3,4-oxadiazol-2-amine hydrobromide salt

Product 1

HCID 591354204-Fluoro-N-{5-[4-(pyridin-3-yloxy)phenyl]-1,3,4-oxadiazol-2-yl}-3-(trifluoromethyl)-benzamideYield 47.3%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 1049PyridineSolvent

Procedure

5-[4-(Pyridin-3-yloxy)phenyl]-1,3,4-oxadiazol-2-amine hydrobromide salt (167.5 mg, 0.5 mmol) was suspended in 2 mL of anhydrous pyridine. Neat 4-fluoro-3-trifluoromethylbenzoyl chloride (200 uL) was added directly into the solution. It was left to stir for 18 hours. The reaction mixture formed a red solution with a yellow precipitate. Then it was diluted with ca. 1 mL of MeOH, filtered through 0.22 u syringe filter and purified by reverse phase preparative HPLC using acetonitrile/water mixture containing 0.01% of TFA. Fractions, containing the product, were combined and partitioned between ca. 40 mL of EtOAc and ca. 40 mL of saturated aqueous NaHCO3. The EtOAc layer was washed with brine, dried over anhydrous sodium sulfate and filtered. Solvent was removed in vacuo to give the title product as a yellow solid (105.1 mg). Yield 47.3%.

Workup

  1. waitIt was left
  2. customThe reaction mixture formed a red solution with a yellow precipitate
  3. filtrationfiltered through 0.22 u syringe
  4. filtrationfilter
  5. custompurified by reverse phase preparative HPLC
  6. additioncontaining 0.01% of TFA
  7. additionFractions, containing the product
  8. custompartitioned between ca. 40 mL of EtOAc and ca. 40 mL of saturated aqueous NaHCO3
  9. washThe EtOAc layer was washed with brine
  10. dry with materialdried over anhydrous sodium sulfate
  11. filtrationfiltered
  12. customSolvent was removed in vacuo

Sources & evidence

ORD record
ord-cb6ec36528c041d79eb19b6d9d9666b6
Source dataset
uspto-grants-2013_02
Patent number
US08372971B2

Linked notes

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