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

To a solution of dimethyl (3,3-difluoro-2-oxoheptyl)phosphonate (1) (0.243 g, 941 mmol) in t-butyl methyl ether (4 ml), lithium hydroxide monohydrate (38.2 mg, 910 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) (0.250 g, 627 mmol) in t-butyl methyl ether (3 ml) was added thereto, and the mixed solution was heat refluxed for approximately 42 hours. After cooling to room temperature, the reaction mixture was added to water and extracted twice with t-butyl methyl ether. The organic layers were combined, sequentially washed with saturated sodium bicarbonate water 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 FL-60D: 100 g; ethyl acetate:hexane =1:3), 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) (0.173 g; 326 mmol; yield: 52.0%).

1. temperaturethe mixed solution was heat
2. temperaturerefluxed for approximately 42 hours
3. temperatureAfter cooling to room temperature
4. extractionextracted twice with t-butyl methyl ether
5. washsequentially washed with saturated sodium bicarbonate water and saturated aqueous sodium chloride
6. dry with materialdried with anhydrous magnesium sulfate
7. concentrationAfter concentration under reduced pressure
8. customthe residue was purified by silica gel column chromatography (Fuji Silysia FL-60D: 100 g; ethyl acetate:hexane =1:3)

ORD record

ord-666edd15f9fc40b69ce9253f3062b3be

Source dataset

uspto-grants-2012_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08236969B2