Hydrochloric Acid → 4-(2-Fluoro-5-hydroxy-4-methylanilino)-7-methoxy-6-methoxycarbonylquinoline

HRID 393668Notes

Reaction equation

HRID 393668 reaction equation
Cl[C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:16][CH3:17])=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1.[F:18][C:19]1[CH:25]=[C:24]([CH3:26])[C:23]([OH:27])=[CH:22][C:20]=1[NH2:21].Cl>C1(O)CCCCC1.CCOCC>[F:18][C:19]1[CH:25]=[C:24]([CH3:26])[C:23]([OH:27])=[CH:22][C:20]=1[NH:21][C:2]1[C:11]2[C:6](=[CH:7][C:8]([O:16][CH3:17])=[C:9]([C:12]([O:14][CH3:15])=[O:13])[CH:10]=2)[N:5]=[CH:4][CH:3]=1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 101540985-Amino-4-fluoro-2-methylphenolHCID 22646520Methyl 4-chloro-7-methoxyquinoline-6-carboxylate

Product 1

HCID 226465924-(2-Fluoro-5-hydroxy-4-methylanilino)-7-methoxy-6-methoxycarbonylquinoline

Reagents, catalysts & solvents 2

HCID 3283Diethyl EtherSolventHCID 7966CyclohexanolSolvent

Conditions

Temperature
100 °C

Procedure

A suspension of 4-chloro-7-methoxy-6-methoxycarbonylquinoline (0.252 g, 1 mmol), (prepared as described for the starting material in Example 55), and 2-fluoro-5-hydroxy-4-methylaniline (0.15 g, 1.2 mmol), (prepared as described for the starting material in Example 1), in cyclohexanol (5 ml) containing 1M ethereal hydrogen chloride (1.2 ml) was heated at 100° C. for 2 hours. The mixture was cooled to ambient temperature and diluted with ether. The solid was collected by filtration then absorbed onto silica using methylene chloride/methanol (1/1) containing ammonium hydroxide (1 ml). The product was eluted with methylene chloride/methanol (100/0 increasing to 94:6). Removal of the solvent by evaporation and trituration of the solid with ether followed by collection of the solid by filtration gave 4-(2-fluoro-5-hydroxy-4-methylanilino)-7-methoxy-6-methoxycarbonylquinoline as a cream solid. (195 mg, 54%).

Workup

  1. custom(prepared
  2. custom(prepared
  3. temperatureThe mixture was cooled to ambient temperature
  4. filtrationThe solid was collected by filtration
  5. customthen absorbed onto silica
  6. additioncontaining ammonium hydroxide (1 ml)
  7. washThe product was eluted with methylene chloride/methanol (100/0 increasing to 94:6)
  8. customRemoval of the solvent
  9. customby evaporation and trituration of the solid with ether
  10. filtrationfollowed by collection of the solid by filtration

Sources & evidence

ORD record
ord-e2e64b1765de4842bfd8fc54795c2460
Source dataset
uspto-grants-2004_10
Patent number
US06809097B1

Reaction notes

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