Methanesulfonic Acid → 3'-O-Phenoxyacetylthymidine

Participants

Reaction Steps

To a solution of 5'-O-dimethoxytritylthymidine (27.23 g, 50.0 mmol) in pyridine (100 mL) at 0° C. was added phenoxyacetyl chloride (8.23 mL, 62.5 mL) dropwise, and the mixture was allowed to warm to ambient temperature over 3 hr. The reaction was quenched with methanol (ME, 25 mL) and concentrated in vacuo. The crude product was extracted with dichloromethane (DCM, 300 mL), washed with saturated aqueous sodium bicarbonate (SASB, 300 mL), dried (Na2 SO4), and concentrated. Toluene (2×100 mL) was added, and the solution was concentrated. The residual oil was dissolved in 10% ME in DCM (275 mL) and treated with methanesulfonic acid (3.24 mL, 50.0 mmol). After 30 min the red solution was quenched with SASB (300 mL), and the organic layer was dried (Na2SO4) and concentrated. The crude product was dissolved in 1:1 ethyl acetate (EA): hexanes (H) (250 mL) and precipitated by cooling to -10° C. for 18 h. The mixture was filtered, and the precipitate dried under vacuum to afford 1 (11.4 g, 60.6%). 1H NMR δ 13C NMR (D6DMSO) δ 12.25, 36.41, 61.29, 64.59, 75.57, 83.68, 84.41, 109.75, 114.52, 121.23, 129.48, 135.77, 150.45, 157.54, 163.65, 168.42. HRMS (FAB) calcd. C18 H21N2O7 (MH+) 377.1349; found 377.1355.

Provenance & Evidence