Hydrochloric Acid → HCID 22714681, compound

HRID 351907Notes

Reaction equation

HRID 351907 reaction equation
[O:1]=[C:2]1[CH2:10][CH2:9][CH2:8][C:7]2[NH:6][CH:5]=[C:4]([C:11]([OH:13])=O)[C:3]1=2.C(N(CC)CC)C.ClC(OCC)=O.[F:27][C:28]1[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=1[NH2:30].Cl>CN(C)C=O>[F:27][C:28]1[CH:34]=[CH:33][CH:32]=[CH:31][C:29]=1[NH:30][C:11]([C:4]1[C:3]2[C:2](=[O:1])[CH2:10][CH2:9][CH2:8][C:7]=2[NH:6][CH:5]=1)=[O:13]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 95842-FluoroanilineHCID 10928Ethyl chloroformateHCID 153376324-Oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid

Product 1

HCID 22714681HCID 22714681, compoundYield 64.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of 4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid (538 mg, 3 mmol) and triethylamine (0.88 mL, 6.3 mmol) in N,N-dimethylformamide (15 mL) at 0° C. was added ethyl chloroformate (0.57 mL, 6 mmol). After stirring at 0° C. for 45 minutes, 2-fluoroaniline (0.58 mL, 6 mmol) wad added. The mixture was stirred for an additional 45 minutes, then allowed to stir at ambient temperature for 14 hours. The mixture was poured into aqueous 1.2 N hydrochloric acid and extracted 2× with ethyl acetate. The combined organic layers were washed with water, dried over magnesium sulfate, filtered, and concentrated in vacuo. To the residue was added aqueous 1N sodium hydroxide (10 mL) and ethyl alcohol (2 mL) and the mixture heated at reflux for 4.5 hours. After cooling in an ice water bath, the mixture was acidified with aqueous hydrochloric acid, the precipitate collected, rinsed with water and dried. Recrystallization from ethyl alcohol afforded N-(2-fluorophenyl)-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamide (Compound 46)(530 mg). mp 238-240° C.

Workup

  1. stirringThe mixture was stirred for an additional 45 minutes
  2. stirringto stir at ambient temperature for 14 hours
  3. extractionextracted 2× with ethyl acetate
  4. washThe combined organic layers were washed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. additionTo the residue was added aqueous 1N sodium hydroxide (10 mL) and ethyl alcohol (2 mL)
  9. temperaturethe mixture heated
  10. temperatureat reflux for 4.5 hours
  11. temperatureAfter cooling in an ice water bath
  12. customthe precipitate collected
  13. washrinsed with water
  14. customdried
  15. customRecrystallization from ethyl alcohol

Sources & evidence

ORD record
ord-30b41385a3314ed191abcff9d5a37876
Source dataset
uspto-grants-2004_06
Patent number
US06743817B2

Reaction notes

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