Ammonia → (R)-5-[5-(benzhydrylidene-amino)-2-fluoro-phenyl]-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine

Participants

Reaction Steps

A suspension of (R)-5-[5-(benzhydrylidene-amino)-2-fluoro-phenyl]-5-methyl-morpholine-3-thione [Building block H, step b)] (1.25 g, 3.09 mmol) in methanol (57 ml) was treated with a solution of ammonia in methanol (26.5 ml, 185 mmol) and a solution of tert-butyl-hydroperoxide (4.28 ml, 30.9 mmol). After stirring at room temperature for 40 hours, the reaction mixture was diluted with water and extracted three times with dichloromethane. The combined organic layers were washed with water, dried over sodium sulfate, evaporated, and dried at high vacuum at room temperature to yield the crude (R)-5-[5-(benzhydrylidene-amino)-2-fluoro-phenyl]-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine as a light brown foam which was dissolved in dioxane (20 ml) and treated with hydrochloric acid (1 M, 3.09 ml). After 40 minutes at room temperature the reaction mixtures was diluted with a saturated solution of hydrogen-carbonate and water. The mixture was extracted three times with ethyl acetate, then the aqueous phase basified with a solution of sodium hydroxide (28%). After four extractions with dichloromethane, the organic layers were combined, dried over sodium sulfate and evaporated. The (R)-5-(5-amino-2-fluoro-phenyl)-5-methyl-5,6-dihydro-2H-[1,4]oxazin-3-ylamine was obtained as an off-white waxy solid (445 mg, 64% of theory).

Provenance & Evidence