反応 #970891

ord-69ac27bd847743799158a8c904c56e2c

反応条件

詳細条件
See reaction.notes.procedure_details.

後処理

  1. 1
    温度the mixed solution was heat
  2. 2
    温度refluxed for approximately 48 hours
  3. 3
    温度After cooling to room temperature
  4. 4
    workup.STIRRINGthe mixture was stirred
  5. 5
    その他separated into two layers
  6. 6
    抽出The aqueous layer was extracted twice with ethyl acetate
  7. 7
    洗浄sequentially washed with 3% aqueous sodium chloride and saturated aqueous sodium chloride
  8. 8
    乾燥dried with anhydrous magnesium sulfate
  9. 9
    濃縮After concentration under reduced pressure
  10. 10
    その他the residue was purified by silica gel column chromatography (Fuji Silysia BW-300SP: 36 g/15 g/18 g; ethyl acetate:hexane =1:4) three times

実験手順

To a solution of dimethyl (3,3-difluoro-2-oxoheptyl)phosphonate (1) (1.051 g, 4.070 mmol) in anhydrous t-butyl methyl ether (16 ml), lithium hydride (30.3 mg, 3.81 mmol) was added and the mixture was stirred for approximately 6 hours at room temperature. A solution of methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydro pyranyloxy)cyclopentyl]heptanate (2) (0.903 g, 2.27 mmol) in anhydrous t-butyl methyl ether (3 ml) was added thereto, and the mixed solution was heat refluxed for approximately 48 hours. After cooling to room temperature, water was added to the solution and the mixture was stirred, let to stand and then separated into two layers. The aqueous layer was extracted twice with ethyl acetate. The organic layers were combined, sequentially washed with 3% aqueous sodium chloride and saturated aqueous sodium chloride, and then dried with anhydrous magnesium sulfate. After concentration under reduced pressure, the residue was purified by silica gel column chromatography (Fuji Silysia BW-300SP: 36 g/15 g/18 g; ethyl acetate:hexane =1:4) three times, to give methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((E)-4,4-difluoro-3-oxo-1-octenyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (3) (0.257 g; 0.484 mmol; yield: 21.3%).

出典

DOI: 10.6084/m9.figshare.5104873.v1特許: US08236969B2uspto-grants-2012_08