Water → Tetrahydropyranyl ether

Participants

Reaction Steps

The free acid prepared from the lactol of Preparation 95 which is of the same epimeric configuration at the 3 position of its side chain as the desired configuration at C-15 position of the prostaglandin-type product of this example. The reaction of this part is carried out under an atmosphere of nitrogen with exclusion of moisture. 20 ml. of dimethyl sulfoxide is added to 0.88 g. of a 50 percent sodium hydride dispersion in mineral oil. The mixture is stirred and heated at 70° to 80° C. for 1 hour, then cooled in an ice bath. 4.4 g. of the phosphonium salt of Example A, (3,3-difluoro-4-carboxybutyl)triphenylphosphonium bromide, is added with stirring. The ice bath is removed and stirring is continued for 15 min. 2 g. of the lactol of Preparation 95 dissolved in 5 ml. of dimethyl sulfoxide and 5 ml. of benzene is added dropwise, followed by 10 ml. of benzene. Stirring is continued for 1.5 hr. The reaction mixture is then diluted with 200 ml. of benzene and a solution of 3 g. of potassium bisulfate in 75 ml. of water. The layers are separated and the aqueous layer is extracted twice with 100 ml. of benzene. The organic solutions are combined and washed twice with 50 ml. of water. The water is backwashed with 100 ml. of benzene, and the combined benzene solutions are then dried over sodium sulfate. Filtration and evaporation of solvent yields the bis-tetrahydropyranyl ether of 2,2-difluoro-PGF2α.

Provenance & Evidence