Hydrochloric Acid → Tetrahydropyranyl ether

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Reaction Conditions

Reaction Steps

Refer to Chart E. There is first prepared the bis-tetrahydropyran-2-yl ether of the title compound. A solution of the formula-XLI 3,3aβ ,4,5,6,6aβ -hexahydro-5α-hydroxy-2ξ-(2'-hydroxyethyl-4β-(3'α-hydroxy-trans-1-octenyl)-2H-cyclopenta[b]furan, 3',5-bistetrahydropyran-2-yl ether (Example 5, 0.80 g.) in 10 ml. of dimethyl sulfoxide and 5 ml. of tetrahydrofuran is treated at about 0°-5° C. with 1.1 ml. of 1.6 M n-butyllithium in hexane added dropwise over a one-minute period. Thereafter the mixture is stirred at about 10° C. for 5 min., followed by additions of 8 ml. of dimethylformamide and 0.35 g. of lithium chloroacetate. The mixture is stirred at about 25° C. for 22 hr., then diluted with 125 ml. of ice and water containing 3 ml. of concentrated hydrochloric acid. The resulting mixture is extracted with dichloromethane and the organic phase is washed with cold water and brine, and concentrated. The residue containing the acid form of the formula-LIII bistetrahydropyran-2-yl ether, is converted to the methyl ester in diethyl ether by reaction with diazomethane. After 3 min., the excess diazomethane is destroyed with acetic acid and the mixture is washed with dilute potassium hydroxide solution and brine, dried, and concentrated to yield the formula-LIII bistetrahydropyran-2-yl ether of the title compound, as mixed isomers.

Provenance & Evidence