4-(Trifluoromethyl)benzoic acid → HCID 59509432, compound

HRID 2407479Notes

Reaction equation

HRID 2407479 reaction equation
[F:1][C:2]([F:13])([F:12])[C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][CH:4]=1.CN(C)CCCN=C=NCC.O.ON1C2C=CC=CC=2N=N1.O[NH:37][C:38](=[NH:47])[C:39]1[CH:44]=[CH:43][C:42]([CH2:45][OH:46])=[CH:41][CH:40]=1>CN(C)C=O>[F:12][C:2]([F:1])([F:13])[C:3]1[CH:4]=[CH:5][C:6]([C:7]2[O:9][N:47]=[C:38]([C:39]3[CH:44]=[CH:43][C:42]([CH2:45][OH:46])=[CH:41][CH:40]=3)[N:37]=2)=[CH:10][CH:11]=1

Participants

6

Reactant 4

HCID 99664-(Trifluoromethyl)benzoic acidHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 27960291-Hydroxybenzotriazole hydrateHCID 178513316HCID 178513316, compound

Product 1

HCID 59509432HCID 59509432, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 4-trifluoromethylbenzoic acid (6 g, 0.032 mol), 1-(3-dimethylaminopropyl)-3-ethyl-carbodiimide (6.05 g, 0.0315 mol) and 1-hydroxy-benzotriazole hydrate (4.82 g, 0.032 mol) in N,N-dimethylformamide (30 mL) is stirred at room temperature for 30 minutes. N-Hydroxy-4-hydroxymethylbenzamidine (6.97 g, 90%, 0.038 mol) is added and the reaction mixture is heated at reflux for 3 hrs, then allowed to come to room temperature and solvent is removed under reduced pressure. An aqueous solution (100 mL) of sodium bicarbonate is added to the residue and the aqueous layer is extracted with ethyl acetate (2×100 mL). Combined organic layers are dried over anhydrous sodium sulphate and concentrated under reduced pressure. The residue is purified by column chromatography (silica gel 230-400 mesh, n-hexane:ethyl acetate, 65:35) to give 4-[5-(4-trifluoromethylphenyl)-1,2,4-oxadiazol-3-yl]phenylmethanol.

Workup

  1. temperaturethe reaction mixture is heated
  2. temperatureat reflux for 3 hrs
  3. customto come to room temperature
  4. customsolvent is removed under reduced pressure
  5. additionAn aqueous solution (100 mL) of sodium bicarbonate is added to the residue
  6. extractionthe aqueous layer is extracted with ethyl acetate (2×100 mL)
  7. dry with materialCombined organic layers are dried over anhydrous sodium sulphate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue is purified by column chromatography (silica gel 230-400 mesh, n-hexane:ethyl acetate, 65:35)

Sources & evidence

ORD record
ord-95a3d25684ad4fe6a9af7db3b48b0426
Source dataset
uspto-grants-2014_08
Patent number
US08809539B2

Reaction notes

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