Hydrochloric Acid → HCID 12051607, compound

HRID 276127Notes

Reaction equation

HRID 276127 reaction equation
[O:1]=[C:2]1[CH2:10][C:9]([CH3:12])([CH3:11])[CH2:8][C:7]2[NH:6][CH:5]=[C:4]([C:13]([OH:15])=O)[C:3]1=2.C(N(CC)CC)C.ClC(OCC)=O.[F:29][C:30]1[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=1[NH2:32].Cl>CN(C)C=O>[F:29][C:30]1[CH:36]=[CH:35][CH:34]=[CH:33][C:31]=1[NH:32][C:13]([C:4]1[C:3]2[C:2](=[O:1])[CH2:10][C:9]([CH3:11])([CH3:12])[CH2:8][C:7]=2[NH:6][CH:5]=1)=[O:15]

Participants

7

Reactant 5

HCID 313Hydrochloric AcidHCID 8471TriethylamineHCID 95842-FluoroanilineHCID 10928Ethyl chloroformateHCID 12051606HCID 12051606, compound

Product 1

HCID 12051607HCID 12051607, compoundYield 24.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of 4-oxo-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indole-3-carboxylic acid (155 mg, 0.75 mmol) and triethylamine (209 μL, 1.5 mmol) in dimethylformamide (4 mL) at 0° C. was added ethyl chloroformate (143 μL, 1.5 mmol). After stirring an additional 45 minutes, 2-fluoroaniline (145 μL, 1.5 mmol) was added. The reaction mixture was stirred for 30 minutes, then poured into aqueous 3.6N hydrochloric acid and extracted 2× with ethyl acetate. The combined organic layers were washed with water, dried over magnesium sulfate, filtered, and concentrated it vacuo. To the residue was added aqueous 5N sodium hydroxide (5 mL) and ethyl alcohol (1 mL), and the mixture was heated at reflux for 30 minutes. After cooling in an ice water bath, the reaction mixture was acidified with hydrochloric acid, the precipitate was collected, rinsed with water, and dried to give 55 mg of N-(2-fluorophenyl)-4-oxo-6,6-dimethyl-4,5,6,7-tetrahydro-1H-indole-3-carboxamide (Compound 2).

Workup

  1. stirringThe reaction mixture was stirred for 30 minutes
  2. extractionextracted 2× with ethyl acetate
  3. washThe combined organic layers were washed with water
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated it vacuo
  7. additionTo the residue was added aqueous 5N sodium hydroxide (5 mL) and ethyl alcohol (1 mL)
  8. temperaturethe mixture was heated
  9. temperatureat reflux for 30 minutes
  10. temperatureAfter cooling in an ice water bath
  11. customthe precipitate was collected
  12. washrinsed with water
  13. customdried

Sources & evidence

ORD record
ord-7ebcee800bd64aab9e1e1be3d75908f8
Source dataset
uspto-grants-2002_03
Patent number
US06353109B2

Reaction notes

Loading…