Hydrochloric Acid → 3-Methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

HRID 245245Notes

Reaction equation

HRID 245245 reaction equation
Br[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].[CH3:26][S:27]([O-:29])=[O:28].[Na+].Cl>CS(C)=O.C(OCC)(=O)C.O.[Cu]I>[CH3:22][C:6]1[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)=[N:8][C:9]2[C:4]([C:5]=1[C:23]([OH:25])=[O:24])=[CH:3][C:2]([S:27]([CH3:26])(=[O:29])=[O:28])=[CH:11][CH:10]=2

Participants

8

Reactant 3

HCID 313Hydrochloric AcidHCID 2733271Sodium methanesulfinate2×HCID 673839956-Bromo-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid

Product 1

HCID 673841653-Methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acidYield 45.3%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)Catalyst2×HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
120 °C

Procedure

To a suspension of 6-bromo-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (10 g, 21.94 mmol) in dimethyl sulfoxide (146 mL) was added copper(I) iodide (8.36 g, 43.9 mmol) and sodium methanesulfinate (5.27 g, 43.9 mmol). The reaction mixture was alternately evacuated and purged with nitrogen three times and heated to 120° C. for 18 h. Additional copper(I) iodide (8.36 g, 43.9 mmol) and sodium methanesulfinate (5.27 g, 43.9 mmol) was added, and the mixture was stirred for an additional 22 h. The mixture was cooled to room temperature and diluted with ethyl acetate and water. The mixture was acidified to pH 2-3 with 2N HCl, filtered through Celite®, and rinsed with ethyl acetate. The organic layer was separated, washed with water, dried over MgSO4, filtered, and concentrated in vacuo to give 3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylic acid (4.07 g, 30% yield) as an orange solid. MS (m/z) 410.0 (M+H+).

Workup

  1. customThe reaction mixture was alternately evacuated
  2. custompurged with nitrogen three times
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationfiltered through Celite®
  5. washrinsed with ethyl acetate
  6. customThe organic layer was separated
  7. washwashed with water
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e252b030a9f34f89a16f0d0637e06e23
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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