反応 #970893

反応方程式

methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydro pyranyloxy)cyclopentyl]heptanate

methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate

water

dimethyl (3,3-difluoro-2-oxoheptyl)phosphonate

dimethyl(3,3-difluoro-2-oxoheptyl)phosphonate

lithium hydroxide monohydrate

→

methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-((E)-4,4-difluoro-3-oxo-1-octenyl)-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate

収率 55.8%

溶媒

tetrahydrofuran

tetrahydrofuran

反応条件

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
   濃縮the solution was concentrated under reduced pressure
5. 5
   workup.ADDITIONEthyl acetate and water were added to the residue
6. 6
   workup.STIRRINGthe solution was stirred
7. 7
   その他separated into two layers
8. 8
   抽出The aqueous layer was extracted twice with ethyl acetate
9. 9
   洗浄sequentially washed with 3% aqueous sodium chloride and saturated aqueous sodium chloride
10. 10
    乾燥dried with anhydrous magnesium sulfate
11. 11
    濃縮After concentration under reduced pressure
12. 12
    その他the residue was purified by silica gel column chromatography (Fuji Silysia BW-300SP: 38 g; ethyl acetate:hexane =1:4)

実験手順

A solution of dimethyl (3,3-difluoro-2-oxoheptyl)phosphonate (1) (1.110 g, 4.299 mmol) in tetrahydrofuran (17 ml) was added with lithium hydroxide monohydrate (0.171 g, 4.08 mmol), and the mixture was stirred for approximately 1.2 hours at room temperature. A solution of methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydro pyranyloxy)cyclopentyl]heptanate (2) (0.971 g, 2.44 mmol) in tetrahydrofuran (3 ml), and water (0.32 ml) were added thereto, and the mixed solution was heat refluxed for approximately 48 hours. After cooling to room temperature, the solution was concentrated under reduced pressure. Ethyl acetate and water were added to the residue and the solution 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: 38 g; ethyl acetate:hexane =1:4), 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) (0.722 g; 1.36 mmol; yield: 55.8%).

出典