2,2-Dimethoxypropane → ((3aR,4R,6R,6aS)-6-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-2,2-dimethyltetrahydro-3aH-cyclopenta[d][1,3]dioxol-4-yl)methanol

Participants

Reaction Steps

A mixture of crude (1R,2S,3R,5R)-3-(4-chloro-7H-pyrrolo[2,3-d]pyrimidin-7-yl)-5-(hydroxymethyl)cyclopentane-1,2-diol (10 g, ˜20 mmol, 54% pure by NMR) and 2,2-dimethoxypropane (100 mL, 800 mmol) was treated with p-toluenesulfonic acid monohydrate (7.28 g, 38.3 mmol) and the yellow-brown reaction mixture was stirred vigorously for 1.25 h, at which time the only solids were a fine tan precipitate. HPLC indicated nearly complete consumption of the starting material. The reaction mixture was diluted with water (30 mL) and neutralized with solid NaHCO3 (4.80 g, 57.1 mmol). The volatiles were carefully removed in vacuo and the resulting brown aqueous solution was extracted with EtOAc (3×100 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo to afford a tan paste. Purification by column chromatography (4×22 cm silica; 0-66% EtOAc/Hex) afforded the title compound (4.38 g, 70%, one step) as a colorless foam/glass: MS (ESI+) for C15H18ClN3O3 m/z 324.2 (M+H)+; MS (ESI−) for C15H18ClN3O3 m/z 368.2 (M+HCO2)−; HPLC purity >95% (ret. time, 3.034 min).

Provenance & Evidence