Isatin → 3-Methyl-2-phenylquinoline-4-carboxylic acid

HRID 1071835Notes

Reaction equation

HRID 1071835 reaction equation
[NH:1]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[C:4](=O)[C:2]1=[O:3].[C:12]([C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1)(=O)[CH2:13][CH3:14].[OH-:22].[K+]>C(O)C.O>[CH3:14][C:13]1[C:12]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[N:1][C:11]2[C:6]([C:4]=1[C:2]([OH:22])=[O:3])=[CH:7][CH:8]=[CH:9][CH:10]=2

Participants

6

Reactant 3

HCID 7054IsatinHCID 71481-Phenyl-1-propanoneHCID 14797Potassium Hydroxide

Product 1

HCID 6737103-Methyl-2-phenylquinoline-4-carboxylic acidYield 85%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

A solution of isatin (5.00 g, 34.0 mmol), propiophenone (5.47 g, 5.43 mL, 40.8 mmol), and potassium hydroxide pellets (6.73 g, 102 mmol) in ethanol (40 mL) was stirred at reflux for 23 h. After cooling, the solvent was removed in vacuo to give a brown residue. The residue was dissolved in water (75 mL) and washed with diethyl ether (4×100 mL). The aqueous layer was cooled by the addition of ice (˜50 g) and acidified to pH˜1 via dropwise addition of concentrated HCl with stirring. A solid precipitate was collected by filtration, washed with water and dried to provide the title compound as a yellowish-tan solid (7.59 g, 85%), which was used without further purification. MS (API+): M+1: 264 (45%), 220 (100); %); 1H NMR (300 MHz, DMSO-d6) d 2.39 (s, 3H), 7.49-7.57 (m, 3H), 7.59-7.72 (m, 7.76-7.84 (m, 2H), 8.06 (d, J=8.5 Hz, 1H), 14.20 (v br s, 1H, exchangeable).

Workup

  1. temperatureat reflux for 23 h
  2. temperatureAfter cooling
  3. customthe solvent was removed in vacuo
  4. customto give a brown residue
  5. washwashed with diethyl ether (4×100 mL)
  6. temperatureThe aqueous layer was cooled by the addition of ice (˜50 g)
  7. additionacidified to pH˜1 via dropwise addition of concentrated HCl
  8. filtrationA solid precipitate was collected by filtration
  9. washwashed with water
  10. customdried

Sources & evidence

ORD record
ord-9961680a2fa6484eaec9794223c9a1cb
Source dataset
uspto-grants-2005_06
Patent number
US06906193B2

Reaction notes

Loading…