1,8-Diazabicyclo(5.4.0)undec-7-ene → 3-[(1S)-1-azidoethyl]-5-bromopyridine

HRID 572214

反応式

HRID 572214 の反応式
[Br:1][C:2]1[CH:3]=[C:4]([C@H:8](O)[CH3:9])[CH:5]=[N:6][CH:7]=1.C1(P([N:25]=[N+:26]=[N-:27])(C2C=CC=CC=2)=O)C=CC=CC=1.N12CCCN=C1CCCCC2>O1CCCC1.C(OCC)(=O)C.O>[N:25]([C@H:8]([C:4]1[CH:5]=[N:6][CH:7]=[C:2]([Br:1])[CH:3]=1)[CH3:9])=[N+:26]=[N-:27]

参加物

7

反応物 3

HCID 811841,8-Diazabicyclo(5.4.0)undec-7-eneHCID 199401P,P-Diphenylphosphinic azideHCID 68655864(R)-1-(5-bromopyridin-3-yl)ethanol

生成物 1

HCID 866418603-[(1S)-1-azidoethyl]-5-bromopyridine収率 75%

試薬・触媒・溶媒 3

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒HCID 8857Ethyl Acetate溶媒

実験手順

To a solution of (1R)-1-(5-bromopyridin-3-yl)ethanol (10 mmol) in tetrahydrofuran (40 mL), cooled to 0° C., was added diphenylphosphoryl azide (4.3 mL, 20 mmol) in one portion followed by 1,8-diazabicyclo[5.4.0]undec-7-ene (3 mL, 20 mmol) dropwise over 30 minutes. After this time the reaction mixture was allowed to warm slowly to room temperature and was stirred overnight. The mixture was diluted with ethyl acetate (50 mL) and water (50 mL), the two phases separated and the aqueous phase extracted with ethyl acetate (3×50 mL). The combined organic phases were washed with brine (50 mL), dried (MgSO4) and concentrated under reduced pressure to give a black liquid which was purified by flash chromatography (silica, ethyl acetate/hexanes) to give 3-[(1S)-1-azidoethyl]-5-bromopyridine (1.7 g, 75%) as a colourless liquid. A mixture of m-toluamide (164 mg, 1.21 mmol), 3-[(1S)-1-azidoethyl]-5-bromopyridine (227 mg, 1 mmol), copper (I) iodide (9.6 mg, 0.05 mmol), N,N-dimethylethylene diamine (0.011 mL, 0.1 mmol) and potassium carbonate (276 mg, 2 mmol) in dioxane (1 mL) was heated in a microwave reactor at 110° C. for 30 minutes then at 160° C. for a further 30 minutes. After this time the mixture was allowed to cool to room temperature, was diluted with ethyl acetate (5 mL) and was filtered through Celite. The filtrate was concentrated under reduced pressure to give a brown oil which was purified by flash chromatography (silica, ethyl acetate/dichloromethane) to give N-{5-[(1S)-1-azidoethyl]pyridin-3-yl}-3-methylbenzamide (80 mg, 28%) as a colourless oil.

後処理

  1. customthe two phases separated
  2. extractionthe aqueous phase extracted with ethyl acetate (3×50 mL)
  3. washThe combined organic phases were washed with brine (50 mL)
  4. dry with materialdried (MgSO4)
  5. concentrationconcentrated under reduced pressure
  6. customto give a black liquid which
  7. customwas purified by flash chromatography (silica, ethyl acetate/hexanes)

出典と根拠

ORDレコード
ord-9ed168acf081404598043fd5b69260ee
出典データセット
uspto-grants-2015_05
特許番号
US09029386B2

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