4-Isobutylbenzoic acid → [4-[5-[4-(2-Methylpropyl)phenyl]-1,2,4-oxadiazol-3-yl]phenyl]methanol

HRID 2242232Notes

Reaction equation

HRID 2242232 reaction equation
[CH2:1]([C:5]1[CH:13]=[CH:12][C:8]([C:9]([OH:11])=O)=[CH:7][CH:6]=1)[CH:2]([CH3:4])[CH3:3].C(N1C=CN=C1)(N1C=CN=C1)=O.O[NH:27][C:28](=[NH:37])[C:29]1[CH:34]=[CH:33][C:32]([CH2:35][OH:36])=[CH:31][CH:30]=1>CN(C=O)C.C(OCC)(=O)C>[CH2:1]([C:5]1[CH:6]=[CH:7][C:8]([C:9]2[O:11][N:37]=[C:28]([C:29]3[CH:34]=[CH:33][C:32]([CH2:35][OH:36])=[CH:31][CH:30]=3)[N:27]=2)=[CH:12][CH:13]=1)[CH:2]([CH3:3])[CH3:4]

Participants

6

Reactant 3

HCID 381114-Isobutylbenzoic acidHCID 682631,1'-CarbonyldiimidazoleHCID 178513316HCID 178513316, compound

Product 1

HCID 11645224[4-[5-[4-(2-Methylpropyl)phenyl]-1,2,4-oxadiazol-3-yl]phenyl]methanolYield 29%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of 4-isobutyl-benzoic acid (451 mg, 2.53 mmol) and 1,1′-carbonyldiimidazole (491 mg, 3.03 mmol) in DMF (10 mL) was stirred at room temperature for 2 hours. N-hydroxy-4-hydroxymethyl-benzamidine (420 mg, 2.53 mmol) was added to the reaction mixture, stirred at room temperature for 18 hours and diluted with ethyl acetate. The reaction mixture was washed with aqueous sodium hydroxide (0.25 N), water and brine, dried (MgSO4), filtered and concentrated in vacuo. The resulting residue was treated with a solution of tetrabutylammonium fluoride (1.0 M in THF, 2.78 mL) and THF (6 mL) and stirred at room temperature for 12 hours. The reaction mixture was quenched with brine and extracted with ethyl acetate. The combined organic layers were concentrated in vacuo. Purification by flash chromatography (silica, 1:9 to 2:3 EtOAc:hexanes) provided the title compound (193 mg, 29% yield) as a solid.

Workup

  1. washThe reaction mixture was washed with aqueous sodium hydroxide (0.25 N), water and brine
  2. dry with materialdried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated in vacuo
  5. additionThe resulting residue was treated with a solution of tetrabutylammonium fluoride (1.0 M in THF, 2.78 mL) and THF (6 mL)
  6. stirringstirred at room temperature for 12 hours
  7. customThe reaction mixture was quenched with brine
  8. extractionextracted with ethyl acetate
  9. concentrationThe combined organic layers were concentrated in vacuo
  10. customPurification by flash chromatography (silica, 1:9 to 2:3 EtOAc:hexanes)

Sources & evidence

ORD record
ord-d576ffa97e294571a9130304ac97e270
Source dataset
uspto-grants-2010_03
Patent number
US07671043B2

Reaction notes

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