Phenol → 8-(4-Phenoxy-bicyclo[2.2.2]oct-1-yl)-1,3-dipropyl-3,7-dihydro-purine-2,6-dione

Participants

Reaction Conditions

Reaction Steps

To a solution of 60 mg of 8-(4-Hydroxy-bicyclo[2.2.2]oct-1-yl)-1,3-dipropyl-3,7-dihydro-purine-2,6-dione (Example 13a) (0.167 mmol) in CH2Cl2 (2 ml) was added 27 μL of pyridine and the reaction mixture cooled to 0° C. To this was added 40 μL of triflic anhydride (0.24 mmol) in CH2Cl2 (1 ml). Maintained at 10° C. overnight. The reaction mixture was diluted with CH2Cl2 (5 ml) and washed with cold 1N HCl, sat'd NaHCO3 and brine. Dried over sodium sulfate and concentrated in vacuo to afford a yellow oil. The crude triflate was dissolved in 1,4-dioxane (3 ml) and 100 mg of phenol (1.08 mmol was added followed by heating at 80° C. overnight. The reaction mixture was concentrated down and the residue taken up in ethyl acetate (10 ml) washed with 1N KOH (5 ml), sat'd NaHCO3 (5 ml), 1N HCl (5 ml) and brine. The organic layer was dried over NaSO4 and concentrated in vacuo to a colorless oil which was purified by column chromatography (SiO2, 1:1 hexanes/EtOAc) to afford 11 mg of title compound as a white solid (MH+=437.29). The following compounds were prepared in an analogous manner after saponification of the methyl ester.

Provenance & Evidence