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

HRID 351898

Reaction equation

HRID 351898 reaction equation
[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]

Participants

6

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

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 4-oxo-4,5,6,7-tetrahydroindole-3-carboxylate (125 g). m.p. 269-270° C.

Workup

  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

Sources & evidence

ORD record
ord-3e657af248cf4389ae3d0a137433ebe1
Source dataset
uspto-grants-2004_06
Patent number
US06743817B2

Linked notes

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