Chlorotrimethylsilane → (5R)-4-(4-methoxybenzyl)-5-methylmorpholine

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Reaction Steps

Chlorotrimethylsilane (37 g, 341 mmol) was added to a solution of lithium borohydride (3.7 g, 170 mmol) in tetrahydrofuran (200 ml) and the mixture was stirred for one hour at room temperature. A solution of (5R)-4-(4-methoxybenzyl)-5-methylmorpholin-3-one (19.6 g, 83.3 mmol) in tetrahydrofuran (20 ml) was added to the solution and the mixture was stirred for one hour at room temperature. After careful addition of methanol with ice-cooled solution, pH was adjusted to 12-14 with 6N aqueous potassium hydroxide and the solution was stirred for 2 hours at 80° C. After cooling, the solution was partitioned between water and ethyl acetate. The organic layer was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent; 5-10% methanol in chloroform) to afford (5R)-4-(4-methoxybenzyl)-5-methylmorpholine (17.8 g, 80.3 mmol, 96%) as colorless oil.

Provenance & Evidence