2-Chloro-4'-fluoroacetophenone → 3-[2-(4-fluoro-phenyl)-2-oxo-ethyl]-5-methyl-3H-1,3,4-oxadiazol-2-one

HRID 2381940Notes

Reaction equation

HRID 2381940 reaction equation
[CH3:1][C:2]1[O:6][C:5](=[O:7])[NH:4][N:3]=1.C[O-].[Na+].Cl[CH2:12][C:13]([C:15]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][CH:16]=1)=[O:14]>CO.[Br-].C([N+](CCCC)(CCCC)CCCC)CCC.C(Cl)(Cl)Cl>[F:21][C:18]1[CH:19]=[CH:20][C:15]([C:13](=[O:14])[CH2:12][N:4]2[N:3]=[C:2]([CH3:1])[O:6][C:5]2=[O:7])=[CH:16][CH:17]=1

Participants

7

Reactant 3

HCID 1202482-Chloro-4'-fluoroacetophenoneHCID 53239745-Methyl-2,3-dihydro-1,3,4-oxadiazol-2-oneHCID 10942334Sodium Methoxide

Product 1

HCID 685555493-[2-(4-fluoro-phenyl)-2-oxo-ethyl]-5-methyl-3H-1,3,4-oxadiazol-2-oneYield 100%

Reagents, catalysts & solvents 3

HCID 74236Tetrabutylammonium BromideCatalystHCID 887MethanolSolvent2×HCID 6212ChloroformSolvent

Procedure

To a solution of 5-methyl-3H-1,3,4-oxadiazol-2-one (2.77 g, 27.7 mmol) in MeOH (25 mL) is added 25 wt % NaOMe solution in methanol (6.4 mL, 27.9 mmol) and the mixture is stirred at rt for 10 min. The mixture is concentrated in vacuo and the residue is added to a solution of 2-chloro-4′-fluoroacetophenone (4.71 g, 27.3 mmol) and tetrabutylammonium bromide (0.174 g, 0.54 mmol) in CHCl3 (16 mL). The mixture is heated to reflux for 2.5 h under N2. The reaction mixture is then allowed to cool and stirred overnight at ambient temperature. The resultant slurry is filtered through qualitative filter paper and the filtrate is concentrated to obtain a liquid. This liquid is further filtered through a pad of silica gel, eluting with 1:1 EtOAc/DCM. The filtrate is concentrated in vacuo to afford 3-[2-(4-fluoro-phenyl)-2-oxo-ethyl]-5-methyl-3H-1,3,4-oxadiazol-2-one (˜100%). MS: 237 (M+H); 1H NMR (300 MHz, CDCl3) δ 7.90-8.10 (m, 2H), 7.10-7.22 (m, 2H), 5.08 (s, 2H), 2.29 (s, 3H).

Workup

  1. concentrationThe mixture is concentrated in vacuo
  2. temperatureThe mixture is heated
  3. temperatureto reflux for 2.5 h under N2
  4. temperatureto cool
  5. stirringstirred overnight at ambient temperature
  6. filtrationThe resultant slurry is filtered through qualitative filter paper
  7. concentrationthe filtrate is concentrated
  8. customto obtain a liquid
  9. filtrationThis liquid is further filtered through a pad of silica gel
  10. washeluting with 1:1 EtOAc/DCM
  11. concentrationThe filtrate is concentrated in vacuo

Sources & evidence

ORD record
ord-de81ecaf73144023942e7648ea4e3575
Source dataset
uspto-grants-2012_09
Patent number
US08258130B2

Reaction notes

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