Methyl iodide → HCID 67418259, compound

HRID 245221Notes

Reaction equation

HRID 245221 reaction equation
F[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=1)[C:6]([CH3:22])=[C:5]2[C:23]([OH:25])=[O:24].[OH-].[K+].[CH3:28][CH:29]([S-])[CH3:30].[Na+].[CH3:33]I.O[O:36][S:37]([O-:39])=O.[K+]>O.CO>[CH3:22][C:6]1[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:19])([F:21])[F:20])[CH:13]=2)=[N:8][C:9]2[C:4]([C:5]=1[C:23]([O:25][CH3:33])=[O:24])=[CH:3][C:2]([S:37]([CH:29]([CH3:30])[CH3:28])(=[O:39])=[O:36])=[CH:11][CH:10]=2

Participants

8

Reactant 5

HCID 6328Methyl iodideHCID 14797Potassium HydroxideHCID 3470666Sodium 2-propanethiolateHCID 23707502Potassium hydroxy sulfiteHCID 673838086-Fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Product 1

HCID 67418259HCID 67418259, compoundYield 97.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent3×

Conditions

Temperature
100 °C

Procedure

6-Fluoro-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (90 g, 258 mmol) was treated with KOH (14.48 g, 258 mmol) in water. The solution was concentrated and azeotroped with toluene (three times). The resulting solid was dissolved in dimethyl sulfoxide (1 L) and sodium 2-propanethiolate (57.0 g, 581 mmol) was added. The mixture was heated to 100° C. and stirred overnight. The solution was cooled to room temperature and MeI (0.048 L, 774 mmol) was added. After stirring for 1 h, water (500 mL) was added slowly with stirring. The solid precipitate was collected by filtration, washed with water, and dried. The filter cake was dissolved in tetrahydrofuran (1.5 L) and cooled in an ice bath. Oxone (317 g, 516 mmol) was added as a solution in water (1.5 L). The ice bath was removed, and stirring was continued for 2 h. The organic phase was separated, and the aqueous phase was extracted with methylene chloride (three times). The THF and methylene chloride extracts were combined, concentrated to approximately 1 L, diluted with methylene chloride (500 mL), and washed with brine. The organic phase was concentrated to afford a brown residue. Methanol was added and the solution was heated to reflux with stirring. The mixture was cooled to room temperature and stirred overnight. The precipitate was collected by filtration, washed with methanol, and dried under reduced pressure to afford methyl 3-methyl-6-[(1-methylethyl)sulfonyl]-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (114 g, 97% yield) as an off-white solid. 1H NMR (400 MHz, METHANOL-d4) 68.29-8.36 (m, 2H), 8.17 (d, J=8.78 Hz, 1H), 7.97 (s, 1H), 7.91 (d, J=7.53 Hz, 1H), 7.85 (d, J=7.78 Hz, 1H), 7.76 (t, J=7.78 Hz, 1H), 4.13 (s, 3H), 3.47 (quin, J=6.71 Hz, 1H), 2.45 (s, 3H), 1.30 (s, 3H), 1.28 (s, 3H); MS (m/z) 452.1 (M+H+).

Workup

  1. concentrationThe solution was concentrated
  2. customazeotroped with toluene (three times)
  3. dissolutionThe resulting solid was dissolved in dimethyl sulfoxide (1 L)
  4. temperatureThe solution was cooled to room temperature
  5. stirringAfter stirring for 1 h
  6. stirringwith stirring
  7. filtrationThe solid precipitate was collected by filtration
  8. washwashed with water
  9. customdried
  10. dissolutionThe filter cake was dissolved in tetrahydrofuran (1.5 L)
  11. temperaturecooled in an ice bath
  12. customThe ice bath was removed
  13. stirringstirring
  14. waitwas continued for 2 h
  15. customThe organic phase was separated
  16. extractionthe aqueous phase was extracted with methylene chloride (three times)
  17. concentrationconcentrated to approximately 1 L
  18. additiondiluted with methylene chloride (500 mL)
  19. washwashed with brine
  20. concentrationThe organic phase was concentrated
  21. customto afford a brown residue
  22. temperaturethe solution was heated
  23. temperatureto reflux
  24. stirringwith stirring
  25. temperatureThe mixture was cooled to room temperature
  26. stirringstirred overnight
  27. filtrationThe precipitate was collected by filtration
  28. washwashed with methanol
  29. customdried under reduced pressure

Sources & evidence

ORD record
ord-ddd1ce2fef3b44848b2635ddbb6c15f4
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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