Реакция #970892

Уравнение реакции

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

Выход 59.8%

Растворители

tetrahydrofuran

tetrahydrofuran

Условия реакции

Обработка

1. 1
   Температураthe mixed solution was heat
2. 2
   Температураrefluxed for approximately 48 hours
3. 3
   ТемператураAfter cooling to room temperature
4. 4
   Другоеapproximately half of the solvent was evaporated from the solution under reduced pressure
5. 5
   workup.ADDITIONEthyl acetate and water were added to the solution
6. 6
   workup.STIRRINGthe solution was stirred
7. 7
   Другоеseparated into two layers
8. 8
   ЭкстракцияThe aqueous layer was extracted twice with ethyl acetate
9. 9
   Промывкаsequentially washed with 3% aqueous sodium chloride and saturated aqueous sodium chloride
10. 10
    Сушкаdried with anhydrous magnesium sulfate
11. 11
    КонцентрированиеAfter concentration under reduced pressure
12. 12
    Другоеthe residue was purified by silica gel column chromatography (Fuji Silysia BW-300SP 27 g, ethyl acetate:hexane =1:4)
13. 13
    workup.ADDITIONThe fractions containing impurities
14. 14
    Другоеwere re-purified by silica gel column chromatography (Fuji Silysia BW-300SP: 6 g; ethyl acetate:hexane=1:4)

Методика

To a solution of dimethyl (3,3-difluoro-2-oxoheptyl)phosphonate (1) (1.050 g, 4.066 mmol) in tetrahydrofuran (16 ml), lithium hydroxide monohydrate (0.161 g, 3.84 mmol) was added and the mixture was stirred at room temperature for approximately 1.2 hours. A solution of methyl 7-[(1R,2R,3R,5S)-5-acetoxy-2-formyl-3-(2-tetrahydropyranyloxy)cyclopentyl]heptanate (2) (0.903 g, 2.27 mmol) in tetrahydrofuran (3 ml), and water (0.57 ml) were added thereto, and the mixed solution was heat refluxed for approximately 48 hours. After cooling to room temperature, approximately half of the solvent was evaporated from the solution under reduced pressure. Ethyl acetate and water were added to the solution 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 27 g, ethyl acetate:hexane =1:4). The fractions containing impurities were re-purified by silica gel column chromatography (Fuji Silysia BW-300SP: 6 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) (0.719 g; 1.35 mmol; yield: 59.8%).

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