Methyl iodide → Methyl 3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

HRID 245146Notes

Reaction equation

HRID 245146 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]([O:25][CH3:26])=[O:24].[CH3:27][S:28]([O-:30])=[O:29].[Na+].IC>[Cu]I.O>[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]([O:25][CH3:26])=[O:24])=[CH:3][C:2]([S:28]([CH3:27])(=[O:30])=[O:29])=[CH:11][CH:10]=2

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 2733271Sodium methanesulfinateHCID 67383812Methyl 6-bromo-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

Product 1

HCID 67383507Methyl 3-methyl-6-(methylsulfonyl)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylateYield 64%

Reagents, catalysts & solvents 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

Methyl 6-bromo-3-methyl-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (50 g, 118 mmol) was combined with copper(I) iodide (44.9 g, 236 mmol) and sodium methylsulfinate (24.07 g, 236 mmol) in a 2 L round bottom flask and the vessel was purged with N2 (3×). The solids were suspended in dimethyl sulfoxide (400 mL), the atmosphere was exchanged for nitrogen (3×Vac/N2 purges), and the reaction was heated to 120° C. overnight. The reaction was cooled to 50° C., and iodomethane (50.2 g, 354 mmol) was added. The reaction was stirred for 2 hours at 50° C. and cooled to RT. The crude reaction mixture was added slowly 1 L of water with stirring over 30 minutes. The resulting yellow slurry was filtered through a buchner funnel. The filter cake was washed with 3×500 mL water and dried overnight. The solids were suspended in 625 mL CH2Cl2, and the suspension was stirred for ca. 30 min. The solids were purified by flash chromatography eluting with 100% CH2Cl2→40% EtOAc/CH2Cl2. Fractions containing the product were further purified by trituration with MeOH. Mixed fractions were repurified using the same conditions and combined with the previously isolated solid to provide 31.9 g (64%) of the product as a white solid. MS (m/z) 423.7 (M+H+).

Workup

  1. customthe vessel was purged with N2 (3×)
  2. temperatureThe reaction was cooled to 50° C.
  3. temperaturecooled to RT
  4. customThe crude reaction mixture
  5. stirringwith stirring over 30 minutes
  6. filtrationThe resulting yellow slurry was filtered through a buchner funnel
  7. washThe filter cake was washed with 3×500 mL water
  8. customdried overnight
  9. stirringthe suspension was stirred for ca. 30 min
  10. customThe solids were purified by flash chromatography
  11. washeluting with 100% CH2Cl2
  12. additionFractions containing the product
  13. customwere further purified by trituration with MeOH
  14. customMixed fractions were repurified

Sources & evidence

ORD record
ord-88909529f3de4cf49c48c08511117841
Source dataset
uspto-grants-2014_02
Patent number
US08658636B2

Reaction notes

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