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

HRID 2381940ノート

反応式

HRID 2381940 の反応式
[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

参加物

7

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 3

HCID 74236Tetrabutylammonium Bromide触媒HCID 887Methanol溶媒2 回HCID 6212Chloroform溶媒

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-de81ecaf73144023942e7648ea4e3575
出典データセット
uspto-grants-2012_09
特許番号
US08258130B2

反応ノート

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