p-Chlorophenethylic alcohol → HCID 58661638, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-chloro-2′,3′,5′-tris-O-(triisopropylsilyl)adenosine (Example 6, 5.0 g) and 15 ml of 2-(4-chlorophenyl)ethyl alcohol was purged with nitrogen and heated to 50° C. Sodium hydride (1.56 g, 60% dispersion in mineral oil) was added at a rate so as to control gas evolution. After 48 hours of heating LC and LC/MS analysis showed a mixture of products with one and two protecting groups respectively (2 isomers). The reaction mixture was allowed to cool to room temperature and carefully quenched with 40 mL of water. The resulting mixture was extracted with ethyl acetate (70 ml). The layers were separated and the aqueous layer was again extracted with ethyl acetate (2×50 mL). The combined organic phases were washed with brine (80 mL), dried over MgSO4 and concentrated under reduced pressure to afford a clear oil (18 g). This was purified by silica gel chromatography eluting progressively with CH2Cl2, 1%, 2%, 5% and then 10% MeOH in CH2Cl2. The fractions containing the desired products were combined and concentrated to yield 3.2 g of a gummy white solid. This mixture of silylated displacement products was taken to the next step.

Provenance & Evidence