Methyl iodide → Methyl 3-methyl-6-[(1-methylethyl)sulfonyl]-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245202Notes

Reaction equation

HRID 245202 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][C:11]=1[O:12][CH3:13])[N:8]=[C:7]([C:14]1[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:23])([F:22])[F:21])[CH:15]=1)[C:6]([CH3:24])=[C:5]2[C:25]([O:27][CH3:28])=[O:26].[CH:29]([S:32]([O-:34])=[O:33])([CH3:31])[CH3:30].[Na+].IC>CS(C)=O.C(Cl)Cl.O.[Cu]I>[CH3:24][C:6]1[C:7]([C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([C:20]([F:22])([F:21])[F:23])[CH:15]=2)=[N:8][C:9]2[C:4]([C:5]=1[C:25]([O:27][CH3:28])=[O:26])=[CH:3][C:2]([S:32]([CH:29]([CH3:31])[CH3:30])(=[O:34])=[O:33])=[C:11]([O:12][CH3:13])[CH:10]=2

Participants

8

Reactant 3

HCID 6328Methyl iodideHCID 23685748Sodium propane-2-sulfinateHCID 67384067Methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 67383265Methyl 3-methyl-6-[(1-methylethyl)sulfonyl]-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 90.1%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (10.0 g, 22.01 mmol) in dimethyl sulfoxide (200 mL) was added copper(I) iodide (8.39 g, 44.0 mmol) and sodium isopropanesulfinate (5.73 g, 44.0 mmol). The mixture was evacuated, purged with N2 three times, and heated at 120° C. overnight. The mixture was cooled to room temperature, treated with iodomethane (4.13 mL, 66.0 mmol), and stirred for 1 h. The reaction mixture was diluted with methylene chloride (150 mL) and water (150 mL), stirred for 30 min, and filtered through Celite®. The filtrate was extracted with methylene chloride, and the organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated. The material was purified via column chromatography (ISCO, 0-30% ethyl acetate/methylene chloride) to give methyl 3-methyl-6-[(1-methylethyl)sulfonyl]-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (9.55 g, 90% yield). 1H NMR (400 MHz, DMSO-d6) δ8.24 (s, 1H), 7.99-8.05 (m, 2H), 7.91 (s, 1H), 7.76-7.84 (m, 2H), 4.09 (s, 6H), 3.83 (quin, J=6.84 Hz, 1H), 2.37 (s, 3H), 1.21 (s, 3H), 1.20 (s, 3H); MS (m/z) 482.1 (M+H+).

Workup

  1. customThe mixture was evacuated
  2. custompurged with N2 three times
  3. temperatureThe mixture was cooled to room temperature
  4. stirringstirred for 30 min
  5. filtrationfiltered through Celite®
  6. extractionThe filtrate was extracted with methylene chloride
  7. washthe organic phase was washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe material was purified via column chromatography (ISCO, 0-30% ethyl acetate/methylene chloride)

Sources & evidence

ORD record
ord-f60dd02d0952439f95e08ed0b9e7553d
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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