Sodium hydride → (5-Ethyl-2,6-dimethoxy-pyrimidin-4-yl)-(3-hydroxymethyl-5-methyl-phenyl)-methanone

Participants

Reaction Steps

To a stirred solution of [3-(tert-butyl-dimethyl-silanyloxymethyl)-5-methyl-phenyl]-(5-ethyl-2,6-dimethoxy-pyrimidin-4-yl)-acetonitrile (3.74 g, 8.47 mmol) in anhydrous DMF (40 ml), was added 60% sodium hydride (373 mg, 9.32 mmol). After 20 min., oxygen was bubbled into the reaction mixture for 3 hr. The mixture was partitioned between ether and aqueous saturated ammonium chloride solution. The ether layer was taken, washed with water twice, dried with anhydrous magnesium sulfate, filtered, and evaporated in vacuo. The residue was stirred with p-toluenesulfonic acid monohydrate (152 mg, 0.8 mmol) in methanol (10 ml) for 2 hr. at room temperature. The mixture was evaporated in vacuo and the residue was purified by silica gel column chromatography (eluent, ether: hexanes (from 1:1 to 3:2)) to afford 1.59 g (59%) of a white solid. m.p. 101-103° C.; 1H NMR (200 MHz, CDCl3) δ 1.05 (3H, t, J=7.4 Hz), 2.35-2.48 (5H, m), 3.93 (3H, s), 4.06 (3H, s), 4.63 (2H, br. S), 7.40 (1H, s), 7.56 (1H, s), 7.60 (1H, s).

Provenance & Evidence