Sodium hydride → 4-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-6-chloropyrimidine

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Reaction Conditions

Reaction Steps

A flame-dried 50 mL round bottom flask with was charged with sodium hydride (0.322 g, 0.008 mol) and tetrahydrofuran (20 mL, 0.3 mol) and the resulting suspension was cooled to 0° C. under an atmosphere of nitrogen. To the suspension was added dropwise a solution of (1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentanol (13) (1.45 g, 0.004 mol) in 0.5 mL THF at 0° C. The mixture was stirred at 0° C. for 10 minutes, at which point 4,6-dichloropyrimidine (0.659 g, 0.004 mol) was added, and the mixture was allowed to warm to room temperature and stirred for 18 hours. The reaction was quenched with via addition of saturated aqueous NH4Cl solution (25 mL) and transferred to a separatory funnel. The layers were separated, and the aqueous layer was extracted with tert-BuOMe (3×25 mL). The combined organic layers were washed with brine, dried over anhydrous MgSO4, filtered, and concentrated in vacuo. The resulting oil was purified by silica gel chromatography (eluent—0-10% EtOAc in hexanes) to afford 4-{[(1R,3S,4S)-3-{[tert-butyl(dimethyl)silyl]oxy}-4-({[tert-butyl(dimethyl)silyl]oxy}methyl)cyclopentyl]oxy}-6-chloropyrimidine (1.75 g, 92% yield). LCMS: (FA) ES+ 473; 1H NMR (300 MHz, CDCl3) δ 8.55 (d, J=0.7, 1H), 6.69 (d, J=0.8, 1H), 5.61-5.49 (m, 1H), 4.36 (dd, J=4.6, 6.8, 1H), 3.73 (dd, J=7.0, 10.0, 1H), 3.57 (dd, J=6.7, 9.9, 1H), 2.36-2.13 (m, 2H), 2.10-1.73 (m, 3H), 0.89 (s, 9H), 0.88 (s, 9H), 0.08-0.00 (m, 12H).

Provenance & Evidence