1-Hydroxybenzotriazole hydrate → 4-[5-(3-Chloro-4-cyclohexylphenyl)-1,2,4-oxadiazol-3-yl]benzenemethanol

HRID 1777356Notes

Reaction equation

HRID 1777356 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1)[C:5]([OH:7])=O.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:3]=[C:4]([C:5]2[O:7][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:8]=[CH:9][C:10]=1[CH:11]1[CH2:16][CH2:15][CH2:14][CH2:13][CH2:12]1

Participants

5

Reactant 3

HCID 27960291-Hydroxybenzotriazole hydrateHCID 203104163-Chloro-4-cyclohexylbenzoic acidHCID 178513316HCID 178513316, compound

Product 1

HCID 708694564-[5-(3-Chloro-4-cyclohexylphenyl)-1,2,4-oxadiazol-3-yl]benzenemethanol

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
132.5 °C

Procedure

N,N-Dicyclohexylcarbodiimide (0.615 g, 0.003 mol) is added to a solution of 3-chloro-4-cyclohexyl benzoic acid (0.475 g, 0.002 mol), N-hydroxy-4-hydroxymethylbenzamidine (0.45 g, 0.003 mol) and N-hydroxybenzotriazole monohydrate (0.457 g, 0.003 mol) in N,N-dimethylformamide (10 mL). The reaction mixture is stirred at 130-135° C. for 2 hrs. It is then cooled to 0-5° C., filtered and washed with dichloromethane (2×20 mL). The filtrate is evaporated under reduced pressure and the residue is treated with demineralized water (20 mL). It is extracted with ethyl acetate (3×15 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, 15:85) to give {4-[5-(3-chloro-4-cyclohexylphenyl)-[1,2,4]-oxadiazol-3-yl]phenyl}methanol.

Workup

  1. temperatureIt is then cooled to 0-5° C.
  2. filtrationfiltered
  3. washwashed with dichloromethane (2×20 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 (3×15 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, 15:85)

Sources & evidence

ORD record
ord-e34a51f808bb4e75ae0fc33c4daf3307
Source dataset
uspto-grants-2016_02
Patent number
US09266867B2

Reaction notes

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