Triphenylphosphine → 9-((3aS,4R,6R,6aR)-6-(azidomethyl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)-6-chloro-9H-purine

Participants

Reaction Steps

A mixture of ((3aR,4R,6R,6aS)-6-(6-chloro-9H-purin-9-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol (7.9 g, 24 mmol) and polymer-supported triphenylphosphine (3 mmol/g loading; 11 g, 34 mmol) in THF (100 mL) was cooled to 0° C. (ice/brine bath) and treated dropwise with diisopropyl azodicarboxylate (6.7 mL, 34 mmol). The tan slurry was stirred for 15 min, and treated dropwise with a solution of diphenylphosphonic azide (7.3 mL, 34 mmol) in THF (24 mL). The brown reaction mixture was stirred for 18.5 h as the ice bath expired; HPLC indicated conversion to the desired product. At 21.5 h the reaction mixture was filtered, the solids were washed with CH2Cl2, and the filtrate was concentrated in vacuo. The red-brown residue was taken up in CH2Cl2 (300 mL) and washed with saturated aqueous NaHCO3 (1×100 mL), water (1×100 mL), and brine (1×150 mL). The separated organic layer was dried (Na2SO4) and concentrated in vacuo to afford a red-orange oil. Purification by column chromatography (7×16 cm silica; 0-10% acetone/CH2Cl2) afforded the title compound (4.82 g, 57%) as a yellow oil/foam: MS (ESI+) for C14H16ClN7O2 m/z 350.1 (M+H)+; MS (ESI−) for C14H16ClN7O2 m/z 394.1 (M+HCO2)−; HPLC purity >95 area %.

Provenance & Evidence