ethyl 5-fluoro-1H-indole-2-carboxylate → HCID 21914152, compound

HRID 887917Notes

Reaction equation

HRID 887917 reaction equation
[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][C:6]([C:11]([O:13][CH2:14]C)=[O:12])=[CH:5]2>CO>[F:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]([C:11]([O:13][CH3:14])=[O:12])[CH2:5]2

Participants

3

Reactant 1

HCID 2727899ethyl 5-fluoro-1H-indole-2-carboxylate

Product 1

HCID 21914152HCID 21914152, compoundYield 58.9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a suspension of 5-fluoro-1H-indole-2-carboxylic acid, ethyl ester (0.121 mole) in methanol (600 ml) was added Mg (0.36 mole). The mixture was in a 3-neck round bottom flask under argon at room temperature. The temperature of the reaction was monitored closely. After about 10 minutes, the mixture began to bubble, slowly at first and then more vigorously. The reaction temperature was maintained between 15 and 25° C. with intermittent applications of an ice bath. After 30 minutes, the bubbling had slowed. The mixture was allowed to stir at room temperature for three days. The mixture was partitioned between 600 ml of chloroform and 500 ml of saturated NH4Cl solution. The organic layer was dried over MgSO4 and concentrated to a brown oil. The oil was dissolved in ether and extracted with 3N HCl. The aqueous layer was washed with ether, basified with 3N NaOH, and extracted with chloroform. The extract was dried over MgSO4 and concentrated, yielding 13.91 g of methyl 5-fluoro-2,3-dihydro-1H-indole-2-carboxylate (intermediate 16).

Workup

  1. customThe mixture was in a 3-neck round bottom flask under argon at room temperature
  2. customto bubble
  3. temperatureThe reaction temperature was maintained between 15 and 25° C. with intermittent applications of an ice bath
  4. waitAfter 30 minutes
  5. customThe mixture was partitioned between 600 ml of chloroform and 500 ml of saturated NH4Cl solution
  6. dry with materialThe organic layer was dried over MgSO4
  7. concentrationconcentrated to a brown oil
  8. dissolutionThe oil was dissolved in ether
  9. extractionextracted with 3N HCl
  10. washThe aqueous layer was washed with ether
  11. extractionextracted with chloroform
  12. dry with materialThe extract was dried over MgSO4
  13. concentrationconcentrated

Sources & evidence

ORD record
ord-2251fc9d71314ad7bc7db20983767c5f
Source dataset
uspto-grants-2012_08
Patent number
US08247432B2

Reaction notes

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