Dimethyl acetylenedicarboxylate → 2-Methoxycarbonyl-6-chloro-7-methyl-4-oxoquinoline

HRID 6680

Reaction equation

HRID 6680 reaction equation
[Cl:1][C:2]1[CH:8]=[CH:7][C:5]([NH2:6])=[CH:4][C:3]=1[CH3:9].[C:10]([C:16](OC)=[O:17])#[C:11][C:12]([O:14][CH3:15])=[O:13]>CO>[CH3:15][O:14][C:12]([C:11]1[CH2:10][C:16](=[O:17])[C:7]2[C:5](=[CH:4][C:3]([CH3:9])=[C:2]([Cl:1])[CH:8]=2)[N:6]=1)=[O:13]

Participants

4

Reactant 2

HCID 12980Dimethyl acetylenedicarboxylateHCID 235364-Chloro-3-methylaniline

Product 1

HCID 684363462-Methoxycarbonyl-6-chloro-7-methyl-4-oxoquinolineYield 81.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

Alternatively, to a solution of 4-chloro-3-methyl aniline (20.0 g, 0.141 mol) in MeOH (400 mL) was added drop-wise dimethyl acetylenedicarboxylate (21.07 g, 0.148 mol). The reaction mixture was stirred at ambient temperature for 30 minutes. The solvent was removed by evaporation and the residue was added to stirred diphenyl ether (300 mL), which has been preheated to 250° C. After 30 minutes, the mixture was cooled to ambient temperature and the resulting precipitate was collected and washed with 1 L of hot petroleum ether to give a mixture (29.0 g) of 2-methoxycarbonyl-6-chloro-7-methyl-4-oxoquinoline and 2-methoxycarbonyl-6-chloro-5-methyl-4-oxoquinoline as a gray solid. The mixture was dissolved in boiling methanol (1 L) and filtered hot. The collected solids were boiled in 1.2 L of methanol and filtered hot to afford (6.45 g, 16%) of 2-methoxycarbonyl-6-chloro-7-methyl-4-oxoquinoline: 1H NMR (DMSO-d6) 2.41 (s, 3), 3.92 (s, 3), 6.58 (s, 1), 7.86 (s, 1), 7.96 (s, 1) ppm.

Workup

  1. customThe solvent was removed by evaporation
  2. additionthe residue was added
  3. stirringto stirred diphenyl ether (300 mL), which
  4. customhas been preheated to 250° C
  5. waitAfter 30 minutes
  6. temperaturethe mixture was cooled to ambient temperature
  7. customthe resulting precipitate was collected
  8. washwashed with 1 L of hot petroleum ether

Sources & evidence

ORD record
ord-b1946fdbc0c24122be9c85cffe1099fa
Source dataset
uspto-grants-2006_08
Patent number
US07084142B2

Linked notes

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