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

HRID 245260ノート

反応式

HRID 245260 の反応式
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].[CH2:29]([S:31]([OH:33])=[O:32])[CH3:30].[Na].IC>CN1CCCC1=O.CS(C)=O.C(Cl)Cl.O.[Cu]I>[CH2:29]([S:31]([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])(=[O:33])=[O:32])[CH3:30]

参加物

10

反応物 4

HCID 6328Methyl iodide2 回HCID 435496Ethanesulfinic acidHCID 5360545SodiumHCID 67384067Methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate

生成物 1

HCID 67384351Methyl 6-(ethylsulfonyl)-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate収率 76%

試薬・触媒・溶媒 5

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒HCID 962Water溶媒HCID 6344Dichloromethane溶媒HCID 13387N-methyl-2-pyrrolidone溶媒

反応条件

温度
120 °C

実験手順

To a solution of methyl 6-bromo-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (2 g, 4.40 mmol) in N-methyl-2-pyrrolidone (15 mL) and DMSO (30 mL) was added copper(I) iodide (2.52 g, 13.21 mmol) followed by ethanesulfinic acid, sodium salt (1.534 g, 13.21 mmol). The mixture was evacuated and purged with N2 three times and heated at 120° C. for 16 h. The mixture was cooled to room temperature, and iodomethane (1.377 mL, 22.01 mmol) was added. After 90 min, additional iodomethane (1.377 mL, 22.01 mmol) was added and the mixture was stirred for an additional hour. The mixture was diluted with methylene chloride and water, and the biphasic solution was filtered through Celite®. The phases were separated, and the aqueous phase was extracted with methylene chloride (50 mL). The combined organic extracts were washed with water (3×50 mL), dried over MgSO4, filtered and concentrated in vacuo. The residue was loaded onto florisil and purified via column chromatography (ISCO, 40 g silica, 5-55% ethyl acetate/hexanes) to give methyl 6-(ethylsulfonyl)-3-methyl-7-(methyloxy)-2-[3-(trifluoromethyl)phenyl]-4-quinolinecarboxylate (1.95 g, 76% yield). MS (m/z) 468.0 (M+H+).

後処理

  1. customThe mixture was evacuated
  2. custompurged with N2 three times
  3. temperatureThe mixture was cooled to room temperature
  4. filtrationthe biphasic solution was filtered through Celite®
  5. customThe phases were separated
  6. extractionthe aqueous phase was extracted with methylene chloride (50 mL)
  7. washThe combined organic extracts were washed with water (3×50 mL)
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. custompurified via column chromatography (ISCO, 40 g silica, 5-55% ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-ebc50067082e4361af932c9ebc81c048
出典データセット
uspto-grants-2014_02
特許番号
US08658636B2

反応ノート

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