Reaction Steps
In a 2 L round-bottomed flask, 4-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]-oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-6-chloropyrimidine (14) (20.5 g, 0.0433 mol was dissolved in ethanol (647.2 mL, 11.08 mol), and cooled to an internal temp of −45° C. To this was added a precooled (−20° C.) solution of 2% conc. HCl in EtOH (326 mL, 0.0516 mol, prepared by diluting 6.5 mL conc. HCl in 319.5 mL ethanol). The reaction mixture was warmed to −25° C. (to prevent pressure buildup upon capping the flask), and then capped and placed in a freezer at −35° C. The reaction was left to stand at −35° C. for 18 hours. The reaction was quenched with sodium carbonate (13.78 g, 0.1300 mol) (˜3 equiv relative to HCl) as a solution in water (40 mL, 2 mol). The volatiles were removed in vacuo, and the reaction mixture was diluted with CH2Cl2 (750 mL). The solids were filtered and set aside, and the volatiles were removed from the filtrate in vacuo. The resulting aqueous mixture with was diluted with EtOAc (500 mL) and water (200 mL) and transferred to a separatory funnel. The layers were separated, and the aqueous layer was extracted 2×250 mL with EtOAc. The combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. The crude residue was purified by column chromatography (applied to column with ˜50 mL CH2Cl2, 400 g column, eluent 0-40% EtOAc:hexanes over 40 min to afford {(1S,2S,4R)-2-{[tert-butyl(dimethyl)silyl]oxy}-4-[(6-chloropyrimidin-4-yl)oxy]cyclopentyl}methanol (11.2 g, 72%). LCMS: (FA) ES+ 359; 1H NMR (400 MHz, CDCl3) δ 8.56 (app d, J=0.6, 1H), 6.70 (app d, J=0.8, 1H), 5.62-5.54 (m, 1H), 4.56 (dd, J=5.6, 10.9, 1H), 3.86-3.78 (m, 1H), 3.70 (ddd, J=6.0, 7.6, 11.3, 1H), 2.48 (dd, J=4.6, 7.6, 1H), 2.42-2.31 (m, 1H), 2.23 (ddd, J=6.3, 9.8, 14.2, 1H), 2.15-2.09 (m, 2H), 1.89 (ddd, J=1.9, 8.0, 14.3, 1H), 0.91 (s, 9H), 0.12 (s, 3H), 0.11 (s, 3H).
