Dimethyl Disulfide → 4-Fluoro-2-methylsulfanyl-benzoic acid

HRID 897356ノート

反応式

HRID 897356 の反応式
Br[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].Cl[Mg]C.C([Li])CCC.[CH3:20][S:21]SC>C1COCC1>[F:11][C:9]1[CH:8]=[CH:7][C:3]([C:4]([OH:6])=[O:5])=[C:2]([S:21][CH3:20])[CH:10]=1

参加物

6

反応物 4

HCID 12232Dimethyl DisulfideHCID 12681692-Bromo-4-fluorobenzoic acidHCID 178418332HCID 178418332、化合物HCID 178418339Butyllithium

生成物 1

HCID 162280324-Fluoro-2-methylsulfanyl-benzoic acid

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

A solution of 2-bromo-4-fluorobenzoic acid (15 g, 68.5 mmol, Aldrich) in THF (150 mL) under Argon at 0 degrees C. was treated with chloro(methyl)magnesium (5.64 g, 75.34 mmol, 2.94 M in THF) over 5 minutes. The temperature during addition was maintained below 10 degrees C. The resulting solution was cooled to −78 degrees C. and n-butyllithium (9.65 g, 150.7 mmol, 2.5M in hexanes) was added over 10 minutes. The reaction was kept below −65 degrees C. during the addition. The reaction was stirred at −78 degrees C. for 50 minutes. A solution of (methyldithio)methane (38.71 g, 410.9 mmol) in THF (20 mL), precooled to −78 degrees C., was added by cannula. The reaction was stirred for 10 minutes, warmed to zero degrees C. and stirred at zero degrees C. for 2 hours until a solid began to precipitate. The reaction was allowed to warm to 25 degrees C. The material was filtered and the solid partitioned between ethyl acetate (400 mL) and water (400 mL). The water layer was acidified with HCl to pH of less than 1 and then extracted with ethyl acetate (4×500 mL). The organic was dried over Na2SO4, filtered, and reduced to a small volume in vacuo to produce crystals. The crystals were filtered and dried in vacuo to afford the title compound.

後処理

  1. customat 0 degrees C
  2. additionThe temperature during addition
  3. temperaturewas maintained below 10 degrees C
  4. customwas kept below −65 degrees C
  5. additionduring the addition
  6. customprecooled to −78 degrees C
  7. addition, was added by cannula
  8. stirringThe reaction was stirred for 10 minutes
  9. temperaturewarmed to zero degrees C
  10. stirringand stirred at zero degrees C
  11. waitfor 2 hours until a solid began
  12. customto precipitate
  13. temperatureto warm to 25 degrees C
  14. filtrationThe material was filtered
  15. customthe solid partitioned between ethyl acetate (400 mL) and water (400 mL)
  16. extractionextracted with ethyl acetate (4×500 mL)
  17. dry with materialThe organic was dried over Na2SO4
  18. filtrationfiltered
  19. customto produce crystals
  20. filtrationThe crystals were filtered
  21. customdried in vacuo

出典と根拠

ORDレコード
ord-3562edb90af74e54ac2a53b6e13f581e
出典データセット
uspto-grants-2005_07
特許番号
US06921759B2

反応ノート

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