Ethyl 4-bromo-3-methylthiophene-2-carboxylate → Ethyl 5-cyano-3-methylthiophene-2-carboxylate

HRID 2381793ノート

反応式

HRID 2381793 の反応式
Br[C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:4]([CH3:12])[CH:3]=1.BrC1C(C)=C(C(OCC)=O)SC=1.[Cu](C#N)[C:26]#[N:27]>CN(C)C=O>[C:26]([C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[C:4]([CH3:12])[CH:3]=1)#[N:27]

参加物

5

反応物 3

HCID 18347936Ethyl 4-bromo-3-methylthiophene-2-carboxylateHCID 60052343Ethyl 5-bromo-3-methylthiophene-2-carboxylateHCID 178418260HCID 178418260、化合物

生成物 1

HCID 59179684Ethyl 5-cyano-3-methylthiophene-2-carboxylate収率 38%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
150 °C

実験手順

A mixture of ethyl 5-bromo-3-methylthiophene-2-carboxylate and ethyl 4-bromo-3-methylthiophene-2-carboxylate (˜1:4) (7.12 g, 28.60 mmol) and copper cyanide (7.68 g, 85.79 mmol) in anhydrous N,N-dimethylformamide (50 mL) was stirred under nitrogen atmosphere at 150° C. for 5 h. The mixture was allowed to cool to ambient temperature, and then partitioned between ethyl acetate (200 mL) and 14% aqueous ammonium hydroxide (200 mL). The organic layer was washed with 14% aqueous ammonium hydroxide (2×100 mL) and brine (100 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The two regioisomers were separated by column chromatography eluted with 2% ethyl acetate in hexanes to afford the title compound as a colorless solid (0.42 g, 38%): 1H NMR (300 MHz, CDCl3) δ 7.39 (s, 1H), 4.36 (q, J=7.1 Hz, 2H), 2.55 (s, 3H), 1.38 (t, J=7.1 Hz, 3H); MS (ES+) m/z 196.1 (M+1).

後処理

  1. temperatureto cool to ambient temperature
  2. custompartitioned between ethyl acetate (200 mL) and 14% aqueous ammonium hydroxide (200 mL)
  3. washThe organic layer was washed with 14% aqueous ammonium hydroxide (2×100 mL) and brine (100 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe two regioisomers were separated by column chromatography
  8. washeluted with 2% ethyl acetate in hexanes

出典と根拠

ORDレコード
ord-b9a57d55f069498ca14a4e94cd8c10c3
出典データセット
uspto-grants-2012_09
特許番号
US08258160B2

反応ノート

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