4-Hydroxybenzoic acid hydrazide → 4-(5-{[4-Chloro-3-(trifluoromethyl)-phenyl]amino}-1,3,4-oxadiazol-2-yl)phenol

HRID 1994031Notes

Reaction equation

HRID 1994031 reaction equation
[OH:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([NH:8][NH2:9])=[O:7])=[CH:4][CH:3]=1.[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([N:19]=[C:20]=S)=[CH:15][C:14]=1[C:22]([F:25])([F:24])[F:23].CCOC(C)=O.CO>CO.[Hg]=O>[Cl:12][C:13]1[CH:18]=[CH:17][C:16]([NH:19][C:20]2[O:7][C:6]([C:5]3[CH:10]=[CH:11][C:2]([OH:1])=[CH:3][CH:4]=3)=[N:8][N:9]=2)=[CH:15][C:14]=1[C:22]([F:23])([F:24])[F:25]

Participants

6

Reactant 3

HCID 17424-Hydroxybenzoic acid hydrazideHCID 5200261-Chloro-4-isothiocyanato-2-(trifluoromethyl)benzeneHCID 21584119Ethylacetate methanol

Product 1

HCID 1361796924-(5-{[4-Chloro-3-(trifluoromethyl)-phenyl]amino}-1,3,4-oxadiazol-2-yl)phenolYield 60.8%

Reagents, catalysts & solvents 2

HCID 30856Mercuric oxideCatalystHCID 887MethanolSolvent

Procedure

Mercury (II) oxide (yellow) (4.55 g, 21.0 mmol) was suspended in 60 mL of anhydrous MeOH under Ar. A bright-orange suspension was formed. To this suspension was added 4-hydroxybenzoic acid hydrazide (3.20 g, 21.0 mmol) and 4-chloro-3-trifluoromethyl-phenylisothiocyanate (5.0 g, 21.0 mmol). The reaction mixture was refluxed for 2 hours. The solvent was removed in vacuo. The black residue was redissolved in 100 mL of EtOAc and the resulting black suspension was filtered through a short pad of silica gel. The filtrate was mixed with 10 g of dry silica gel and solvent was removed in vacuo. The impregnated silica gel was loaded on silica gel column and the product was separated using a gradient of hexane:ethyl acetate mixture starting from 50:50 ratio and finishing at 0:100. All fractions containing the product were combined; solvent was removed in vacuo to give a grey solid. The solid was heated in 50 mL of 4:1 mixture of EtOAc/MeOH. The formed suspension was cooled down to ambient temperature and filtered to give the title product as a white crystalline solid (4.54 g, 60.7% yield).

Workup

  1. customA bright-orange suspension was formed
  2. temperatureThe reaction mixture was refluxed for 2 hours
  3. customThe solvent was removed in vacuo
  4. dissolutionThe black residue was redissolved in 100 mL of EtOAc
  5. filtrationthe resulting black suspension was filtered through a short pad of silica gel
  6. additionThe filtrate was mixed with 10 g of dry silica gel and solvent
  7. customwas removed in vacuo
  8. customthe product was separated
  9. additionAll fractions containing the product
  10. customsolvent was removed in vacuo
  11. customto give a grey solid
  12. filtrationfiltered

Sources & evidence

ORD record
ord-a7675ce57b0e4442a512f85e22a0f140
Source dataset
uspto-grants-2010_01
Patent number
US07652051B2

Reaction notes

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