5-Bromo-2-methoxypyridine → (6-Methoxypyridin-3-yl)(thiazol-5-yl)methanone

HRID 928740

反応式

HRID 928740 の反応式
[Li]CCCC.Br[C:7]1[CH:8]=[CH:9][C:10]([O:13][CH3:14])=[N:11][CH:12]=1.CON(C)[C:18]([C:20]1[S:24][CH:23]=[N:22][CH:21]=1)=[O:19]>C1COCC1>[CH3:14][O:13][C:10]1[N:11]=[CH:12][C:7]([C:18]([C:20]2[S:24][CH:23]=[N:22][CH:21]=2)=[O:19])=[CH:8][CH:9]=1

参加物

5

反応物 3

HCID 27348955-Bromo-2-methoxypyridineHCID 25307138N-Methoxy-N-methyl-1,3-thiazole-5-carboxamideHCID 178418339Butyllithium

生成物 1

HCID 86715595(6-Methoxypyridin-3-yl)(thiazol-5-yl)methanone

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
0 °C

実験手順

A n-BuLi solution (1.89 mL, 3.03 mmol, 1.6 M solution in hexane) was slowly added to a −78° C. solution of 5-bromo-2-methoxypyridine (0.392 mL, 3.03 mmol) in dry THF (10 mL). After addition, stirring was continued for an additional 40 minutes and N-methoxy-N-methylthiazole-5-carboxamide (0.600 g, 3.48 mmol, Intermediate 11: step a) dissolved in THF (10 mL) was slowly added. The mixture was stirred at −78° C. for 10 minutes then warmed to 0° C. and stirred for 1 hour. The cold solution was quenched with saturated aqueous NH4Cl and warmed to room temperature. H2O was added and layers were separated. The aqueous layer was extracted with EtOAc (3×) and the combined organic extracts washed with brine, dried (Na2SO4), filtered, evaporated in vacuo, preabsorbed onto silica gel and chromatographed (CH2Cl2/EtOAc) to provide product. The pure white solid title compound was precipitated from MeOH, filtered and dried under reduced pressure.

後処理

  1. additionAfter addition
  2. additionwas slowly added
  3. stirringThe mixture was stirred at −78° C. for 10 minutes
  4. stirringstirred for 1 hour
  5. customThe cold solution was quenched with saturated aqueous NH4Cl
  6. temperaturewarmed to room temperature
  7. additionH2O was added
  8. customlayers were separated
  9. extractionThe aqueous layer was extracted with EtOAc (3×)
  10. washthe combined organic extracts washed with brine
  11. dry with materialdried (Na2SO4)
  12. filtrationfiltered
  13. customevaporated in vacuo
  14. custompreabsorbed onto silica gel
  15. customchromatographed (CH2Cl2/EtOAc)
  16. customto provide product
  17. customThe pure white solid title compound was precipitated from MeOH
  18. filtrationfiltered
  19. customdried under reduced pressure

出典と根拠

ORDレコード
ord-9ec3a857f29f4efe82b2365c256bea0a
出典データセット
uspto-grants-2016_03
特許番号
US09290476B2

関連ノート

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