Acetic Anhydride → HCID 15870844, compound

HRID 1584826Notes

Reaction equation

HRID 1584826 reaction equation
F[C:2]1[C:15]([CH3:16])=[C:14]([C:17]2[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=2)[CH2:22][N:21]([S:26]([C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=2)(=[O:28])=[O:27])[CH2:20]3)[C:13]([F:36])=[CH:12][C:3]=1[C:4]([CH2:6][C:7]([O:9][CH2:10][CH3:11])=[O:8])=[O:5].C(OC(=O)C)(=O)C.CO[CH:46](OC)[N:47]([CH3:49])C.Cl.[F:53][CH2:54]CN.C[O-].[Na+].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.C(O)C.CN(C)C=O.O>[F:36][C:13]1[CH:12]=[C:3]2[C:2](=[C:15]([CH3:16])[C:14]=1[C:17]1[CH:18]=[C:19]3[C:23](=[CH:24][CH:25]=1)[CH2:22][N:21]([S:26]([C:29]1[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=1)(=[O:27])=[O:28])[CH2:20]3)[N:47]([CH2:46][CH2:54][F:53])[CH:49]=[C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])[C:4]2=[O:5]

Participants

11

Reactant 6

HCID 7918Acetic AnhydrideHCID 9995Ethanamine, 2-fluoro-, hydrochlorideHCID 11430Potassium CarbonateHCID 78373Dimethylformamide dimethyl acetalHCID 10942334Sodium MethoxideHCID 21220360HCID 21220360, compound

Product 1

HCID 15870844HCID 15870844, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolvent2×HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Procedure

In 2 ml of methylene chloride was dissolved 200 mg of ethyl 2,5-difluoro-3-methyl-4-[2-(p-toluenesulfonyl)isoindolin-5-yl]benzoylacetate, and to this solution were added 76 mg of acetic anhydride and 90 mg of N,N-dimethylformamide dimethyl acetal, after which the resulting mixture was stirred at room temperature for two hours. Thereafter, the solvent was removed by distillation under reduced pressure. The residue obtained was dissolved in 1 ml of ethanol, and a solution of 58 mg of 2-fluoroethylamine hydrochloride and 27 mg of sodium methoxide in 1 ml of ethanol was added to the solution, after which the resulting mixture was stirred at room temperature for 20 minutes. The reaction mixture was concentrated under reduced pressure, and the residue obtained was dissolved in 2 ml of N,N-dimethylformamide, after which 65 mg of potassium carbonate was added to the solution. The resulting mixture was stirred at 100° C. for one hour. The reaction mixture was cooled to room temperature, and thereafter, water was added to the mixture. The resulting precipitate was collected by filtration, and the pale yellow solid obtained was purified by a column chromatography (eluent: n-hexane:ethyl acetate=2:1). And diisopropyl ether was thereafter added thereto, after which the crystals formed were collected by filtration, to obtain 126 mg of colorless, crystalline ethyl 6-fluoro-1-(2-fluoroethyl)-8-methyl-7-[2-(p-toluenesulfonyl)isoindolin-5-yl]-1,4-dihydro-4-oxoquinoline-3-carboxylate.

Workup

  1. customThereafter, the solvent was removed by distillation under reduced pressure
  2. customThe residue obtained
  3. stirringafter which the resulting mixture was stirred at room temperature for 20 minutes
  4. concentrationThe reaction mixture was concentrated under reduced pressure
  5. customthe residue obtained
  6. stirringThe resulting mixture was stirred at 100° C. for one hour
  7. temperatureThe reaction mixture was cooled to room temperature
  8. filtrationThe resulting precipitate was collected by filtration
  9. customthe pale yellow solid obtained
  10. customwas purified by a column chromatography (eluent: n-hexane:ethyl acetate=2:1)
  11. additionAnd diisopropyl ether was thereafter added
  12. customafter which the crystals formed
  13. filtrationwere collected by filtration

Sources & evidence

ORD record
ord-a43b3b6d3f7a423387243198c52e70bb
Source dataset
uspto-grants-1999_08
Patent number
US05935952

Reaction notes

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