Ethyl 2-methyl-beta-oxobenzenepropanoate → 2-(3-(2,5-Difluorophenyl)-1,2,4-oxadiazol-5-yl)-1-o-tolylethanone

HRID 2403223Notes

Reaction equation

HRID 2403223 reaction equation
[O:1]=[C:2]([C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=1[CH3:15])[CH2:3][C:4]([O:6]CC)=O.[F:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[C:24](=[N:26]O)[NH2:25]>C1(C)C=CC=CC=1>[F:16][C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][C:18]=1[C:24]1[N:26]=[C:4]([CH2:3][C:2]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[CH3:15])=[O:1])[O:6][N:25]=1

Participants

4

Reactant 2

HCID 2760276Ethyl 2-methyl-beta-oxobenzenepropanoateHCID 43581602,5-difluoro-N'-hydroxybenzenecarboximidamide

Product 1

HCID 667951112-(3-(2,5-Difluorophenyl)-1,2,4-oxadiazol-5-yl)-1-o-tolylethanone

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

A solution of ethyl 3-oxo-3-o-tolylpropanoate (0.44 mL; 2.5 mmol) and 2,5-difluoro-N′-hydroxybenzenecarboximidamide (JRD-Fluorochemical, 215 mg; 1.25 mmol) in toluene (1.5 mL) was heated to 120° C. 18 hours. The solvent was removed in vacuo and the residue purified by flash chromatography on a Biotage 25+M column, eluting with petrol containing increasing amounts of EtOAc. The residue was triturated with petrol to give the title compound as an off-white solid which was used directly without any further purification. 1H NMR (CDCl3, 400 MHz) δ 11.62‡ (1H, br s), 7.82-7.74 (1H, m), 7.55-7.12 (6H, m), 5.95‡ (1H, s), 4.68* (2H, s), [2.58, 2.55 and 2.47] (3H, s) (compound isolated as a mixture of keto and enol forms and as a mixture of rotamers, *=keto form, ‡=enol form). LC/MS: 315 (M+H)+. HPLC (Method D) Rt=4.28 min (Purity: 98.4%).

Workup

  1. custom18 hours
  2. customThe solvent was removed in vacuo
  3. customthe residue purified by flash chromatography on a Biotage 25+M column
  4. washeluting with petrol containing
  5. temperatureincreasing amounts of EtOAc
  6. customThe residue was triturated with petrol

Sources & evidence

ORD record
ord-45f6571cfde940e6b76689bff2ff5f53
Source dataset
uspto-grants-2014_08
Patent number
US08802663B2

Reaction notes

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