Tetrahydrofuran → 4-Benzylmorpholine

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A solution of N-benzyl diol 4 (1.54 g, 4.02 mmol, 1.0 equiv) in 40.0 mL tetrahydrofuran was stirred at 0° C. for 10 min and was then added via cannula to sodium hydride (254.2 mg, 10.06 mmol, 2.5 equiv). The resulting white suspension was stirred vigorously at 0° C. for 5 min before removing the cooling bath. After 1 hr at 23° C., the reaction suspension was returned to a 0° C. bath for 10 min and N-tosylimidazole (894.5 mg, 4.02 mmol. 1.0 equiv) added in 3 portions over 12 min (gas evolution was observed subsequent to the addition of each portion). After stirring the resulting reaction solution for a further 10 min at 0° C., the cooling bath was again removed. After 1 hr at 23° C., excess sodium hydride was CAREFULLY quenched by the slow addition of 30 mL saturated aqueous ammonium chloride to the reaction suspension at 0° C. The reaction mixture was then partitioned between 340 mL ammounium chloride (sat., aq.) and 370 mL diethyl ether and the organic layer separated and washed further with 1×300 mL water and 1×200 mL brine. The aqueous washes were combined and extracted with 2×200 mL diethyl ether. All of the organic extracts were then combined and dried over sodium sulfate. Concentration of the extracts in vacuo provided a yellow oil, which was purified by flash column chromatography (SiO2, 20% ethyl acetate-hexanes), affording the N-benzyl morpholine product as a yellow oil (926.6 mg, 63%).

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