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Tetrahydrofuran → (R)-2-(3,4-Difluorophenyl)-4-[3-(tert-butyldimethylsiloxy)-1-butoxy]-5-bromo-3(2H)-pyridazinone

HRID 382006
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HRID 382006 반응식
[O:1](C(O)CCC)[Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].[F:24][C:25]1[CH:26]=[C:27]([N:32]2[C:37](=[O:38])[C:36](Br)=[C:35]([Br:40])[CH:34]=[N:33]2)[CH:28]=[CH:29][C:30]=1[F:31].[CH2:41]1[CH2:45][O:44][CH2:43][CH2:42]1>>[F:24][C:25]1[CH:26]=[C:27]([N:32]2[C:37](=[O:38])[C:36]([O:44][CH2:43][CH2:42][C@H:41]([O:1][Si:2]([C:5]([CH3:8])([CH3:7])[CH3:6])([CH3:4])[CH3:3])[CH3:45])=[C:35]([Br:40])[CH:34]=[N:33]2)[CH:28]=[CH:29][C:30]=1[F:31]
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참가 물질

5

반응물 4

HCID 8028Tetrahydrofuran3회HCID 2724254Sodium bis(trimethylsilyl)amideHCID 159418894,5-Dibromo-2-(3,4-difluorophenyl)pyridazin-3(2H)-oneHCID 23051061tert-Butyldimethylsiloxy-1-butanol

생성물 1

HCID 23598336(R)-2-(3,4-Difluorophenyl)-4-[3-(tert-butyldimethylsiloxy)-1-butoxy]-5-bromo-3(2H)-pyridazinone수율 51%

실험 절차

To a stirred, 0° C. solution of the product from Example 545B (3.4 g, 10 mmol) in THF (20 mL) was added 1M sodium bis(trimethylsilyl)amide in THF (12 mL, 12 mmol). The reaction mixture was stirred at room temperature for 0.5 hours, then it was transferred to a stirred, −30° C. solution of 2-(3,4-difluorophenyl)-4,5-dibromo-3(2H)-pyridazinone (3.66 g, 10 mmol) in THF (100 mL). The reaction mixture was stirred at −30° C. for 1 hour, then overnight while warming to room temperature. The reaction was quenched with saturated aqueous ammonium chloride solution (100 mL) and extracted with ethyl acetate (2×100 mL). The organic layer was washed with brine (2×20 mL), then dried (MgSO4), and filtered. The filtrate was concentrated under reduced pressure and the residue was purified by column chromatography (silica gel, 90:10 hexane/ethyl acetate) to provide the title intermediate (2.5 g, 51%).

후처리

  1. stirringThe reaction mixture was stirred at −30° C. for 1 hour
  2. temperatureovernight while warming to room temperature
  3. customThe reaction was quenched with saturated aqueous ammonium chloride solution (100 mL)
  4. extractionextracted with ethyl acetate (2×100 mL)
  5. washThe organic layer was washed with brine (2×20 mL)
  6. dry with materialdried (MgSO4)
  7. filtrationfiltered
  8. concentrationThe filtrate was concentrated under reduced pressure
  9. customthe residue was purified by column chromatography (silica gel, 90:10 hexane/ethyl acetate)

출처 및 근거

ORD 기록
ord-a77db14771ed42bcb9bb31c71dc7defd
출처 데이터셋
uspto-grants-2001_10
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US06307047B1

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