Chloride → 4-[3-(4-Methoxy-phenoxymethyl)-[1,2,4]oxadiazol-5-ylmethyl]-benzoic acid ethyl ester

HRID 1818591Notes

Reaction equation

HRID 1818591 reaction equation
[Cl-].[CH2:2]([O:4][C:5](=[O:16])[C:6]1[CH:11]=[CH:10][C:9]([CH2:12][C:13]([OH:15])=O)=[CH:8][CH:7]=1)[CH3:3].CN(C)C=O.O[NH:23][C:24](=[NH:35])[CH2:25][O:26][C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1>C1C=CC=CC=1>[CH2:2]([O:4][C:5](=[O:16])[C:6]1[CH:7]=[CH:8][C:9]([CH2:12][C:13]2[O:15][N:23]=[C:24]([CH2:25][O:26][C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[N:35]=2)=[CH:10][CH:11]=1)[CH3:3]

Participants

6

Reactant 4

HCID 312ChlorideHCID 6228DimethylformamideHCID 10679857Ethyl 4-(carboxymethyl)benzoateHCID 178492604HCID 178492604, compound

Product 1

HCID 666995654-[3-(4-Methoxy-phenoxymethyl)-[1,2,4]oxadiazol-5-ylmethyl]-benzoic acid ethyl esterYield 31.2%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

Add oxaxyl chloride (1.25 mL, 14 mmol) to 4-carboxymethyl-benzoic acid ethyl ester (365 mg, 1.75 mmol) in benzene (11 mL) and a drop of dimethylformamide at room temperature under argon gas over a 5 minute period. Stir the reaction mixture for 2 hours at room temperature. Concentrate the reaction mixture to an oil. Redissolve the oil in dimethylformamide (10 mL) and N-hydroxy-2-(4-methoxy-phenoxy)-acetamidine (380 mg, 1.9 mmol) is added. Stir the reaction mixture at room temperature for 3 hours. Heat the reaction mixture to 120° C. and stir for 7 hours. After cooling to room temperature, quench the reaction mixture with water and extract with ethyl acetate (3×). Combine the organic layers, wash with brine, dry over sodium sulfate, and concentrate. Purify the residue by flash column chromatography using 20% ethyl acetate/hexane to give the title compound (201 mg, 31%). LC-MS (m/e): 369 (M+1).

Workup

  1. concentrationConcentrate the reaction mixture to an oil
  2. dissolutionRedissolve the oil in dimethylformamide (10 mL)
  3. stirringStir the reaction mixture at room temperature for 3 hours
  4. temperatureHeat the reaction mixture to 120° C.
  5. stirringstir for 7 hours
  6. temperatureAfter cooling to room temperature
  7. customquench the reaction mixture with water
  8. extractionextract with ethyl acetate (3×)
  9. washCombine the organic layers, wash with brine
  10. dry with materialdry over sodium sulfate
  11. concentrationconcentrate
  12. customPurify the residue by flash column chromatography

Sources & evidence

ORD record
ord-2e543e4f29434b6eb7a1e01d2da28093
Source dataset
uspto-grants-2009_10
Patent number
US07598423B2

Reaction notes

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