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

HRID 382006
ノート
印刷プレビュー

反応式

HRID 382006 の反応式
[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]
参加物実験手順後処理出典と根拠反応ノート

参加物

5

反応物 4

HCID 8028Tetrahydrofuran3 回HCID 2724254Sodium bis(trimethylsilyl)amideHCID 159418894,5-Dibromo-2-(3,4-difluorophenyl)pyridazin-3(2H)-oneHCID 23051061tert-Butyldimethylsiloxy-1-butanol

生成物 1

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

実験手順

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%).

後処理

  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)

出典と根拠

ORDレコード
ord-a77db14771ed42bcb9bb31c71dc7defd
出典データセット
uspto-grants-2001_10
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US06307047B1

反応ノート

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