p-Toluenesulfonic acid → HCID 178470642, compound

HRID 1708568Notes

Reaction equation

HRID 1708568 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])=[CH:4][CH:3]=1.[F:14][C:15]1[CH:28]=[CH:27][CH:26]=[CH:25][C:16]=1[C:17]([CH2:19][C:20](OCC)=[O:21])=O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1C=CC=CC=1>[F:14][C:15]1[CH:28]=[CH:27][CH:26]=[CH:25][C:16]=1[C:17]1[CH:19]=[C:20]([OH:21])[C:3]2[C:2](=[CH:7][CH:6]=[C:5]([CH2:8][C:9]([O:11][CH2:12][CH3:13])=[O:10])[CH:4]=2)[N:1]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 225219p-Aminophenylacetic acid ethyl esterHCID 296342Ethyl 3-(2-fluorophenyl)-3-oxopropanoate

Product 1

HCID 178470642HCID 178470642, compoundYield 65.4%

Reagents, catalysts & solvents 1

HCID 241BenzeneSolvent

Procedure

Ethyl p-aminophenylacetate (8 g), ethyl 2-fluorobenzoylacetate (10 g) and p-toluenesulfonic acid (1 g) were dissolved into benzene (150 ml) and, providing Dean Stalk dehydrating apparatus placed molecular sieve (MS 4 angstroms) therein, the solution was refluxed for 4.5 hours under heat. Solvent was distilled off under reduced pressure and water was added to the residue, which was extracted with methylene chloride. The organic layer was washed with water, dried over anhydrous sodium sulfate, and then concentrated. After diphenyl ether (60 ml) was added to the residue, the mixture was stirred at 240° to 250° C. for 30 minutes under heat. After cooling, ether was added and the crystals deposited were collected by filtration to obtain crude ethyl 2-(2-fluorophenyl)-4-hydroxyquinoline-6-acetate (9.5 g). After phosphorus oxychloride (40 ml) was added thereto, the mixture was refluxed for 2 hours under heat. After cooling, this was thrown into ice and extracted with methylene chloride. The organic layer was washed with water, dried over anhydrous sodium sulfate, and concentrated to obtain ethyl 4-chloro-2-(2-fluorophenyl)quinoline-6-acetate (9.2 g). This was dissolved into ethanol (200 ml) and, after 10% palladium carbon (1 g) was added, hydrogenation was conducted at a hydrogen pressure of 40 kg/cm2 and at 80° C. Catalyst was filtered off, the filtrate was concentrated under reduced pressure, and the residue was purified by means of silica gel column chromatography (development solvent: methylene chloride) to obtain aimed product (3.7 g) as a pale yellow oily substance.

Workup

  1. customproviding Dean Stalk
  2. temperaturethe solution was refluxed for 4.5 hours
  3. temperatureunder heat
  4. distillationSolvent was distilled off under reduced pressure and water
  5. additionwas added to the residue, which
  6. extractionwas extracted with methylene chloride
  7. washThe organic layer was washed with water
  8. dry with materialdried over anhydrous sodium sulfate
  9. concentrationconcentrated
  10. additionAfter diphenyl ether (60 ml) was added to the residue
  11. temperatureunder heat
  12. temperatureAfter cooling
  13. additionether was added
  14. filtrationthe crystals deposited were collected by filtration

Sources & evidence

ORD record
ord-018346d4446e4880af3185c650f876b5
Source dataset
uspto-grants-1994_10
Patent number
US05359076

Reaction notes

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