1-Hydroxybenzotriazole hydrate → {4-[5-(2-Chlorobiphenyl-4-yl)-[1,2,4]-oxadiazol-3-yl]-phenyl}-methanol

HRID 1777368Notes

Reaction equation

HRID 1777368 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([OH:10])=O)[CH:5]=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1.O[NH:18][C:19](=[NH:28])[C:20]1[CH:25]=[CH:24][C:23]([CH2:26][OH:27])=[CH:22][CH:21]=1.O.ON1C2C=CC=CC=2N=N1>CN(C)C=O>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]2[O:10][N:28]=[C:19]([C:20]3[CH:25]=[CH:24][C:23]([CH2:26][OH:27])=[CH:22][CH:21]=3)[N:18]=2)[CH:5]=[CH:4][C:3]=1[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1

Participants

5

Reactant 3

HCID 27960291-Hydroxybenzotriazole hydrateHCID 198789252-Chlorobiphenyl-4-carboxylic acidHCID 178513316HCID 178513316, compound

Product 1

HCID 70869544{4-[5-(2-Chlorobiphenyl-4-yl)-[1,2,4]-oxadiazol-3-yl]-phenyl}-methanol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
122.5 °C

Procedure

N,N-Dicyclohexylcarbodiimide (4 g, 0.019 mol) is added to a solution of 2-chlorobiphenyl-4-carboxylic acid (3 g, 0.013 mol), N-hydroxy-4-hydroxymethyl benzamidine (2.9 g, 0.017 mol) and N-hydroxybenzotriazole monohydrate (2.9 g, 0.019 mol) in N,N-dimethylformamide (40 mL). The reaction mixture is heated at 120-125° C. for 3 hrs. It is then cooled to 0-5° C., filtered and washed with dichloromethane (2×15 mL). The filtrate is evaporated under reduced pressure and the residue is treated with demineralized water (20 mL). It is extracted with ethyl acetate (2×20 mL) and the combined extract is dried over sodium sulfate. Removal of solvent under reduced pressure gives a crude residue which is purified by column chromatography (silica gel 230-400, ethyl acetate:toluene, 1:9) to give {4-[5-(2-chlorobiphenyl-4-yl)-[1,2,4]-oxadiazol-3-yl]-phenyl}-methanol.

Workup

  1. temperatureIt is then cooled to 0-5° C.
  2. filtrationfiltered
  3. washwashed with dichloromethane (2×15 mL)
  4. customThe filtrate is evaporated under reduced pressure
  5. additionthe residue is treated with demineralized water (20 mL)
  6. extractionIt is extracted with ethyl acetate (2×20 mL)
  7. extractionthe combined extract
  8. dry with materialis dried over sodium sulfate
  9. customRemoval of solvent under reduced pressure
  10. customgives a crude residue which
  11. customis purified by column chromatography (silica gel 230-400, ethyl acetate:toluene, 1:9)

Sources & evidence

ORD record
ord-6b39e34ee45440bda0a8134e31ed2c55
Source dataset
uspto-grants-2016_02
Patent number
US09266867B2

Reaction notes

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