5-Bromo-1-methyl-1H-imidazole → (1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone

HRID 627484ノート

反応式

HRID 627484 の反応式
Br[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.CON(C)[C:11](=[O:22])[C:12]1[CH:17]=[CH:16][C:15]([C:18]([F:21])([F:20])[F:19])=[N:14][CH:13]=1>C1COCC1>[CH3:7][N:6]1[C:2]([C:11]([C:12]2[CH:13]=[N:14][C:15]([C:18]([F:21])([F:19])[F:20])=[CH:16][CH:17]=2)=[O:22])=[CH:3][N:4]=[CH:5]1

参加物

4

反応物 2

HCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 23116945N-methoxy-N-methyl-6-(trifluoromethyl)nicotinamide2 回

生成物 1

HCID 86715442(1-Methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
5.300000190734863 °C

実験手順

To a 3 L 4-neck flask equipped with an overhead stirrer, nitrogen bubbler, and thermocouple was added 5-bromo-1-methyl-1H-imidazole (47.96 g, 297.9 mmol), followed by THF (537 mL). To this room temperature solution was added isopropylmagnesium chloride/lithium chloride complex [1.3 M] (246.8 mL, 320.8 mmol) (addition temperature maintained between 16.6 and 25° C.) to afford a milky suspension and the reaction was stirred for 60 minutes and then cooled to 5.3° C. in an ice bath. To this mixture was added a solution of N-methoxy-N-methyl-6-(trifluoromethyl)nicotinamide (53.66 g, 229.14 mmol, Intermediate 15, step b) in THF (268.3 mL) (addition temperature between 5.3 and 5.6° C.) to afford an orange mixture. After addition, the reaction was warmed to room temperature over 2 hours. After stirring at room temperature for 18 hours, THF (200 mL) was added and the reaction was stirred for 2 hours. The reaction was then cooled to 4° C. with an ice bath and carefully quenched with 2N HCl to a pH=7, quenching temperature reached 12° C. The mixture was diluted with ethyl acetate (500 mL), phase split and the organic layer was washed with brine (2×200 mL) and dried over sodium sulfate, filtered, and the solvent was removed. Hot ether was added and then filtered to give the title compound as a solid.

後処理

  1. customTo a 3 L 4-neck flask equipped with an overhead stirrer
  2. additionTo this room temperature solution was added isopropylmagnesium chloride/lithium chloride complex [1.3 M] (246.8 mL, 320.8 mmol) (addition temperature maintained between 16.6 and 25° C.)
  3. customto afford a milky suspension
  4. customto afford an orange mixture
  5. additionAfter addition
  6. temperaturethe reaction was warmed to room temperature over 2 hours
  7. stirringAfter stirring at room temperature for 18 hours
  8. stirringthe reaction was stirred for 2 hours
  9. temperatureThe reaction was then cooled to 4° C. with an ice bath
  10. customcarefully quenched with 2N HCl to a pH=7
  11. customquenching temperature
  12. customreached 12° C
  13. additionThe mixture was diluted with ethyl acetate (500 mL), phase
  14. customsplit
  15. washthe organic layer was washed with brine (2×200 mL)
  16. dry with materialdried over sodium sulfate
  17. filtrationfiltered
  18. customthe solvent was removed
  19. additionHot ether was added
  20. filtrationfiltered

出典と根拠

ORDレコード
ord-db790b6364ca4b8f8a1a98ebfa498822
出典データセット
uspto-grants-2016_04
特許番号
US09309222B2

反応ノート

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