Ethyl 3-chloro-3-oxopropionate → Ethyl 2-(3-(2,5-difluorophenyl)-1,2,4-oxadiazol-5-yl)acetate

HRID 2403227Notes

Reaction equation

HRID 2403227 reaction equation
Cl[C:2](=[O:9])[CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5].[F:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=1[C:18](=[N:20]O)[NH2:19]>N1C=CC=CC=1>[F:10][C:11]1[CH:16]=[CH:15][C:14]([F:17])=[CH:13][C:12]=1[C:18]1[N:20]=[C:2]([CH2:3][C:4]([O:6][CH2:7][CH3:8])=[O:5])[O:9][N:19]=1

Participants

4

Reactant 2

HCID 118931Ethyl 3-chloro-3-oxopropionateHCID 43581602,5-difluoro-N'-hydroxybenzenecarboximidamide

Product 1

HCID 66795474Ethyl 2-(3-(2,5-difluorophenyl)-1,2,4-oxadiazol-5-yl)acetateYield 770.5%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Ethyl 3-chloro-3-oxopropanoate (1.7 mL; 13.2 mmol) was added to 2,5-difluoro-N′-hydroxybenzenecarboximidamide (JRD-Fluorochemical, 1.13 g; 0.6 mmol) in pyridine (30 mL). The mixture was heated to reflux for 4 hours and the solvent removed in vacuo. The residue was taken up into DCM (20 mL) and washed with water (10 mL). The organic phase was passed through a hydrophobic frit and the solvent removed in vacuo. The residue was purified on a Biotage 25+M column, eluting with petrol containing increasing amounts of EtOAc to give ethyl 2-(3-(2,5-difluorophenyl)-1,2,4-oxadiazol-5-yl)acetate (1.24 g, 70%).

Workup

  1. temperatureThe mixture was heated
  2. temperatureto reflux for 4 hours
  3. customthe solvent removed in vacuo
  4. washwashed with water (10 mL)
  5. customthe solvent removed in vacuo
  6. customThe residue was purified on a Biotage 25+M column
  7. washeluting with petrol containing
  8. temperatureincreasing amounts of EtOAc

Sources & evidence

ORD record
ord-19a3b229db82428ea527059c66bede4d
Source dataset
uspto-grants-2014_08
Patent number
US08802663B2

Reaction notes

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