Ammonium Chloride → N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-N-(2,4-dimethoxybenzyl)-4-fluorobenzenesulfonamide

HRID 46296

反応式

HRID 46296 の反応式
[Cl:1][C:2]1[S:6][C:5]([NH:7][CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=2[O:17][CH3:18])=[N:4][CH:3]=1.C[Si](C)(C)N[Si](C)(C)C.[Li].[C:29]([C:31]1[CH:32]=[C:33]([S:38](Cl)(=[O:40])=[O:39])[CH:34]=[CH:35][C:36]=1[F:37])#[N:30].[Cl-].[NH4+]>O1CCCC1.O>[Cl:1][C:2]1[S:6][C:5]([N:7]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][C:10]=2[O:17][CH3:18])[S:38]([C:33]2[CH:34]=[CH:35][C:36]([F:37])=[C:31]([C:29]#[N:30])[CH:32]=2)(=[O:39])=[O:40])=[N:4][CH:3]=1

参加物

7

反応物 4

HCID 25517Ammonium ChlorideHCID 27789083-Cyano-4-fluorobenzenesulfonyl chlorideHCID 57426343Lithium bis(trimethylsilyl)amideHCID 577321515-chloro-N-(2,4-dimethoxybenzyl)-1,3-thiazol-2-amine

生成物 1

HCID 59436479N-(5-Chloro-1,3-thiazol-2-yl)-3-cyano-N-(2,4-dimethoxybenzyl)-4-fluorobenzenesulfonamide収率 57%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-70 °C

実験手順

Under an atmosphere of nitrogen, 5-chloro-N-(2,4-dimethoxybenzyl)-1,3-thiazol-2-amine (Preparation 208, 3.0 g 10.5 mmol) was dissolved in tetrahydrofuran (20 ml) and cooled to −70° C. Lithium hexamethyldisilazane (1 M in tetrahydrofuran, 12.6 ml, 12.6 mmol) was added dropwise, keeping the temperature below −60° C. After 5 minutes, the cooling bath was removed and the reaction warmed to room temperature, stirred for a further 5 minutes then cooled back to −70° C. 3-Cyano-4-fluorobenzenesulfonyl chloride (2.54 g, 11.6 mmol) in tetrahydrofuran (10 ml) was added dropwise keeping the temperature below −60° C. and the reaction mixture was warmed to room temperature. Saturated aqueous ammonium chloride solution (50 ml) was added followed by water to dissolve the solid which had precipitated out. The aqueous layer was extracted with ethyl acetate (50 ml) and the organic extracts dried over magnesium sulphate and decolourising charcoal, filtered through Celite™ and the filtrate evaporated in vacuo. The resulting gum was purified using a short column (silica gel, 150 g) eluting with ethyl acetate:heptane (1:1, by volume) affording a gum which was triturated with tert-butyl ether, filtered, washed with heptane and dried in vacuo to give the title compound as a buff solid, 2.84 g, 57% yield.

後処理

  1. customthe temperature below −60° C
  2. customthe cooling bath was removed
  3. temperaturethe reaction warmed to room temperature
  4. temperaturethen cooled back to −70° C
  5. customthe temperature below −60° C.
  6. temperaturethe reaction mixture was warmed to room temperature
  7. dissolutionto dissolve the solid which
  8. customhad precipitated out
  9. extractionThe aqueous layer was extracted with ethyl acetate (50 ml)
  10. dry with materialthe organic extracts dried over magnesium sulphate
  11. filtrationfiltered through Celite™
  12. customthe filtrate evaporated in vacuo
  13. customThe resulting gum was purified
  14. washeluting with ethyl acetate:heptane (1:1, by volume)
  15. customaffording a gum which
  16. customwas triturated with tert-butyl ether
  17. filtrationfiltered
  18. washwashed with heptane
  19. customdried in vacuo

出典と根拠

ORDレコード
ord-2d8a4c236074466fa5095d418d783941
出典データセット
uspto-grants-2013_09
特許番号
US08541588B2

関連ノート

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