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

HRID 623950

반응식

HRID 623950 반응식
Br[C:2]1[N:6]([CH3:7])[CH:5]=[N:4][CH:3]=1.C([Mg]Cl)(C)C.[Cl-].[Li+].CON(C)[C:18](=[O:29])[C:19]1[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[N:21][CH:20]=1>C1COCC1>[CH3:7][N:6]1[C:2]([C:18]([C:19]2[CH:20]=[N:21][C:22]([C:25]([F:28])([F:26])[F:27])=[CH:23][CH:24]=2)=[O:29])=[CH:3][N:4]=[CH:5]1

참가 물질

5

반응물 3

HCID 15152585-Bromo-1-methyl-1H-imidazoleHCID 23116945N-methoxy-N-methyl-6-(trifluoromethyl)nicotinamide2회HCID 178461733HCID 178461733, 화합물

생성물 1

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

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매3회

반응 조건

온도
5.300000190734863 °C

실험 절차

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 (246.8 mL, 320.8 mmol, 1.3 M in THF) (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 2, 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 2 N aqueous HCl to pH=7, quenching temperature reached 12° C. The mixture was diluted with ethyl acetate (500 mL), phase separated 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.

후처리

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

출처 및 근거

ORD 기록
ord-8fe5b24718a64695a8de1ed80e6e820d
출처 데이터셋
uspto-grants-2016_04
특허 번호
US09303015B2

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