Benzene → Tetrahydropyranyl ether

Temperature

20 °C

Sodium hydride (0.57 g., 57 percent in mineral oil) in 25 ml. of dimethylsulfoxide, is added to 3 g. of 4,4-difluoro-4-carboxybutyltriphenylphosphonium bromide. The reaction mixture is maintained at 20° C. with stirring for 30 min. A solution of 3α,5α-dihydroxy-2β-[(3R)-3-hydroxy-4-phenoxytrans-1-butenyl]-1α-cyclopentaneacetaldehyde γ-lactol bis-(tetrahydropyranyl ether), 1.57 g., in 10 ml. of dimethylsulfoxide is added. The reaction mixture is stirred at ambient temperature for 2 hr. and diluted with 50 ml. of benzene. Potassium bisulfate (2.7 g. in 30 ml. of water) is slowly added, maintaining the reaction temperature at less than or equal to 10° C. The aqueous layer is extracted with 50 ml. of benzene and the organic extracts are washed successively with 50 ml. of water and 50 ml. of brine before combining, drying, and evaporating. Evaporation yields an oil which is chromatographed on 100 g. of acid washed silica gel packed in 20 percent ethyl acetate and Skellysolve B. Elution with 20-75 percent ethyl acetate and Skellysolve B yields crude 2,2-difluoro-16-phenoxy-17,18,19,20-tetranor-PGF2α, bis-(tetrahydropyranyl ether).

1. stirringThe reaction mixture is stirred at ambient temperature for 2 hr
2. additionand diluted with 50 ml
3. temperaturemaintaining the reaction temperature at less than or equal to 10° C
4. extractionThe aqueous layer is extracted with 50 ml
5. washof benzene and the organic extracts are washed successively with 50 ml
6. customdrying
7. customevaporating
8. customEvaporation
9. customyields an oil which
10. customis chromatographed on 100 g
11. washof acid washed silica gel
12. washElution with 20-75 percent ethyl acetate and Skellysolve B

ORD record

ord-92a24c7b6a46477e95f9a3611fe92c6c

Source dataset

uspto-grants-1977_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04055602