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3,5-Dibromopyridine → [2-(5-Bromopyridin-3-yl)-2-azabicyclo[3.1.0]hex-3-yl]methanol

HRID 241599
ノート
印刷プレビュー

反応式

HRID 241599 の反応式
[Si]([O:18][CH2:19][CH:20]1[NH:24][C:23](=O)[CH2:22][CH2:21]1)(C(C)(C)C)(C1C=CC=CC=1)C1C=CC=CC=1.[Br:26][C:27]1[CH:28]=[N:29][CH:30]=[C:31](Br)[CH:32]=1.[CH3:34]C(C)([O-])C.[Na+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.C(=O)(O)[O-].[Na+].C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[Br:26][C:27]1[CH:32]=[C:31]([N:24]2[CH:20]([CH2:19][OH:18])[CH2:21][CH:22]3[CH:23]2[CH2:34]3)[CH:30]=[N:29][CH:28]=1
参加物反応条件実験手順後処理出典と根拠反応ノート

参加物

8

反応物 4

HCID 693693,5-DibromopyridineHCID 634876Binap, (A+-)-HCID 23676156Sodium t-butoxideHCID 580115465-(tert-Butyldiphenylsiloxymethyl)pyrrolidine-2-one

生成物 1

HCID 67297729[2-(5-Bromopyridin-3-yl)-2-azabicyclo[3.1.0]hex-3-yl]methanol収率 33%

試薬・触媒・溶媒 3

HCID 9811564
Bis(dibenzylideneacetone)palladium
触媒
HCID 312751,4-Dioxane溶媒
HCID 516892Sodium Bicarbonate溶媒

反応条件

温度
110 °C

実験手順

To a stirred solution of (2-Azabicyclo[3.1.0]hex-3-yl)methanol (750 mg, 6.63 mmol) (obtained in step (i)) in dry 1,4-dioxan (20 mL) in a pressure reaction vessel was added 3,5-dibromopyridine (1.57 grams, 6.63 mmol), sodium tert-butoxide (700 mg, 7.3 mmol) and racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (207 mg, 0.33 mmol). The reaction mixture was degassed for 30 minutes, then tris(dibenzylideneacetone)dipalladium (0) (122 mg, 0.133 mmol) was added. The screw cap was fixed on the reaction vessel, the temperature of the reaction was gradually increased to 110° C. and the reaction mixture was stirred at this temperature for 16 hours. The reaction mixture was cooled to room temperature diluted with saturated sodium bicarbonate and extracted with ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, the solvent was removed under reduced pressure and the crude product was purified by 230-400 silica gel flash column chromatography to obtain title compound of 600 mg as solid. Yield: 33%.

後処理

  1. customThe reaction mixture was degassed for 30 minutes
  2. customThe screw cap
  3. temperatureThe reaction mixture was cooled to room temperature
  4. extractionextracted with ethyl acetate
  5. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
  6. customthe solvent was removed under reduced pressure
  7. customthe crude product was purified by 230-400 silica gel flash column chromatography

出典と根拠

ORDレコード
ord-e28703a6b21743028431e44ce439ac68
出典データセット
uspto-grants-2014_02
DOI
10.6084/m9.figshare.5104873.v1
特許番号
US08653071B2

反応ノート

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