反応 #87479

ord-d6d5b1f3def849d68028b09b3407c755

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    温度the reaction mixture was heated
  2. 2
    温度at reflux under nitrogen
  3. 3
    その他The layers were separated
  4. 4
    抽出the aqueous layer was extracted two additional times with dichloromethane (25 mL)
  5. 5
    洗浄The combined organic layers were washed with brine (20 mL)
  6. 6
    乾燥dried over magnesium sulfate
  7. 7
    ろ過filtered through a pad of celite
  8. 8
    濃縮concentrated under reduced pressure
  9. 9
    その他The crude material was chromatographed with the Biotage SP4 automated chromatography unit (SNAP 25 g silica gel column)
  10. 10
    洗浄eluting with a gradient of 0-80% ethyl acetate in heptane

実験手順

To a solution of acetic acid (1R,2S,3S,4R,5S)-3,4-diacetoxy-1-acetoxymethyl-5-[4-chloro-3-(4-ethoxy-benzyl)-phenyl]-6,8-dioxa-bicyclo[3.2.1]oct-2-yl ester (Example 2; 344 mg, 0.569 mmol) in carbon tetrachloride (8 mL) was added N-bromosuccinimide (159 mg, 0.893 mmol) followed by the addition of 2,2′-azobisisobutyronitrile (AIBN, 8 mg, 0.05 mmol) and the reaction mixture was heated at reflux under nitrogen. After 16 hours, the reaction mixture was cooled to room temperature, water (50 mL) and dichloromethane (25 mL) were added and the resulting mixture was stirred for 24 hours at room temperature. The layers were separated and the aqueous layer was extracted two additional times with dichloromethane (25 mL). The combined organic layers were washed with brine (20 mL), dried over magnesium sulfate, filtered through a pad of celite, and concentrated under reduced pressure. The crude material was chromatographed with the Biotage SP4 automated chromatography unit (SNAP 25 g silica gel column) eluting with a gradient of 0-80% ethyl acetate in heptane to produce 316 mg (89% yield) of acetic acid (1R,2S,3S,4R,5S)-3,4-diacetoxy-1-acetoxymethyl-5-{4-chloro-3-[(4-ethoxy-phenyl)-hydroxy-methyl]-phenyl}6,8-dioxa-bicyclo[3.2.1]oct-2-yl ester as a mixture of diastereoisomers at the bis-benzylic position.

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US09439901B2uspto-grants-2016_09