反応 #970889

反応方程式

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

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 90.1%

溶媒

water

t-butyl methyl ether

water

t-butyl methyl ether

反応条件

後処理

1. 1
   温度the mixture was heat
2. 2
   温度refluxed for approximately 49 hours (internal temperature: approximately 53° C.)
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 (200 ml)
7. 7
   洗浄washed twice with saturated aqueous sodium chloride (300 ml)
8. 8
   乾燥dried with anhydrous magnesium sulfate (50 g)
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-300: 1805 g; ethyl acetate:hexane =1:4)
11. 11
    workup.ADDITIONThe fractions containing impurities
12. 12
    その他were re-purified by silica gel column chromatography (Fuji Silysia BW-300: 580 g; ethyl acetate:hexane =1:4)

実験手順

To a solution of dimethyl(3,3-difluoro-2-oxoheptyl)phosphonate (1) (50.50 g, 195.6 mmol) in t-butyl methyl ether (750 ml), lithium hydroxide monohydrate (7.94 g, 189 mmol) was added and the mixture was stirred for one hour at room temperature. A solution of methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (2) (52.00 g, 130.5 mmol) in t-butyl methyl ether (150 ml) and water (27 ml) were added thereto, and the mixture was heat refluxed for approximately 49 hours (internal temperature: approximately 53° C.). After cooling to room temperature, water (300 ml) was added and the mixture was stirred, let to stand and then separated into two layers. The aqueous layer was extracted twice with ethyl acetate (200 ml). The organic layers were combined, washed twice with saturated aqueous sodium chloride (300 ml), and dried with anhydrous magnesium sulfate (50 g). After concentration under reduced pressure, the residue was purified by silica gel column chromatography (Fuji Silysia BW-300: 1805 g; ethyl acetate:hexane =1:4). The fractions containing impurities were re-purified by silica gel column chromatography (Fuji Silysia BW-300: 580 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) (62.38 g; 117.6 mmol; yield: 90.1%) as a pale yellow oil.

出典