Iodoethane → Ethyl 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid

HRID 2215841

反応式

HRID 2215841 の反応式
[O:1]=[C:2]1[C:7]2[C:8]([C:11]([OH:13])=[O:12])=[CH:9][O:10][C:6]=2[CH2:5][CH2:4][CH2:3]1.C(=O)([O-])[O-].[K+].[K+].C(=O)([O-])[O-].[Cs+].[Cs+].I[CH2:27][CH3:28]>CN(C)C=O>[CH2:27]([C:9]1[O:10][C:6]2[CH2:5][CH2:4][CH2:3][C:2](=[O:1])[C:7]=2[C:8]=1[C:11]([OH:13])=[O:12])[CH3:28]

参加物

6

反応物 4

HCID 6340IodoethaneHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 7139374-Oxo-4,5,6,7-tetrahydro-1-benzofuran-3-carboxylic acid

生成物 1

HCID 21953055Ethyl 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid収率 86.9%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

To a stirred mixture of 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid (640 g, 3.55 mol), potassium carbonate (1.7 kg, 10.65 mol) and cesium carbonate (100 g, 0.32 mol) in N,N-dimethylformamide (9.0 L) is added iodoethane (1250 g, 8.01 mol). The mixture is heated at 60° C. for 2 h. After cooling to ambient temperature, the mixture is filtered, the solid is rinsed with ethyl acetate, and the filtrate concentrated in vacuo. Water (2 L) is added then extracted with ethyl acetate (2×2 L); the combined organic extracts are washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to give ethyl 4-oxo-4,5,6,7-tetrahydrobenzofuran-3-carboxylic acid (642 g). A mixture of this ester (640 g, 3.07 mol) and ammonium acetate (426 g, 5.53 mol) in N,N-dimethylformamide (320 mL) is heated to 100° C. for 2 h. The reaction mixture is concentrated in vacuo, ice water (2.5 L) is added, and extracted with dichloromethane (2×3 L); the combined organic extracts are washed with brine, dried over magnesium sulfate, filtered, and concentrated in vacuo to give ethyl 4-oxo-4,5,6,7-tetrahydroindole-3-carboxylate (357 g). A mixture of this ester (170 g, 0.82 mol) in ethyl alcohol (250 mL) and a solution of sodium hydroxide (165 g, 4.1 mol) in water (1 L) is heated at reflux for 1 h, then cooled in an ice water bath. Concentrated hydrochloric acid (350 mL) is added dropwise, the precipitate collected by filtration, rinsed with ice water (3×), and dried in a vacuum oven at 75° C. to afford 125 g of 4-oxo-4,5,6,7-tetrahydroindole-3-carboxylate. m.p. 269-270 C.

後処理

  1. temperatureAfter cooling to ambient temperature
  2. filtrationthe mixture is filtered
  3. washthe solid is rinsed with ethyl acetate
  4. concentrationthe filtrate concentrated in vacuo
  5. additionWater (2 L) is added
  6. extractionthen extracted with ethyl acetate (2×2 L)
  7. washthe combined organic extracts are washed with brine
  8. dry with materialdried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

出典と根拠

ORDレコード
ord-572c6633179f45f88364b75ca2240c0a
出典データセット
uspto-grants-2006_09
特許番号
US07109351B1

関連ノート

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