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

HRID 1272050Notes

Reaction equation

[C:1]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)(=O)[CH2:2][CH3:3].[NH:11]1[C:21]2[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=2)[C:14](=O)[C:12]1=[O:13].[OH-:22].[K+]>C(O)C>[CH3:3][C:2]1[C:1]([C:5]2[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=2)=[N:11][C:21]2[C:16]([C:14]=1[C:12]([OH:22])=[O:13])=[CH:17][CH:18]=[CH:19][CH:20]=2

Participants

Conditions

Temperature: 80 °C

Procedure

3-Methyl-2-phenylquinoline-4-carboxylic acid was prepared by a Pfitzinger reaction (J. Org. Chem. 1950, 15:511–516). Propiophenone (3.3 mL, 1.2 equiv.) was added to a solution of isatin (3.00 g, 20.0 mmol) in ethanol (95%, 30 mL), followed by the addition of KOH pellets (86%, 3.91 g, 3 equiv.). The light brown mixture was stirred at 80° C. (oil bath temperature) for 40 hours. Solvent was removed in vacuo and the resulting solid residue was dissolved in water (50 mL), extracted with ether (30 mL×2) to remove any un-reacted starting materials. The aqueous layer was then cooled with an ice bath and acidified with concentrated aqueous HCl until pH˜3. The white precipitate was collected by suction filtration, washed with water and dried in a vacuum oven (30° C.) overnight. The white solid was essentially pure carboxylic acid (5.10 g, 97% yield) and was used for the next step without further purification. 1H NMR (300 MHz, DMSO-d6) δ 7.50–8.08 (m, 9H), 2.46 (s, 3H).

Workup

customSolvent was removed in vacuo
dissolutionthe resulting solid residue was dissolved in water (50 mL)
extractionextracted with ether (30 mL×2)
customto remove any un-reacted
temperatureThe aqueous layer was then cooled with an ice bath
filtrationThe white precipitate was collected by suction filtration
washwashed with water
customdried in a vacuum oven (30° C.) overnight

Sources & evidence

ORD record: ord-d8bc8d4148f94241b0d40cf270327a41
Source dataset: uspto-grants-2007_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07208502B2

Reaction notes

Loading…