Sodium Hydroxide → (2S)-tert-butyl 2-(4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)morpholine-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

A solution of (2S)-tert-butyl 2-(4-carbamoylphenyl)morpholine-4-carboxylate (intermediate 17, 20.9 g, 68.2 mmol) in N,N-dimethylacetamide dimethyl acetal (110 ml) was stirred at 100° C. for 1 hour. After the mixture was concentrated under reduced pressure, 1,4-dioxane (120 ml), acetic acid (120 ml), 1N-sodium hydroxide (70 ml) and hydroxylamine hydrochloride (4.80 g 69.1 mmol) was added to the residue and the solution was stirred at 100° C. for 2 hours. The mixture was partitioned between water and ethyl acetate, and the organic layer was washed with brine and aqueous sodium hydrogen carbonate and dried over sodium sulfate. The organic solvent was removed under reduced pressure, and the residue was purified by silica gel column chromatography (eluent; hexane/ethyl acetate=6/1) to afford (2S)-tert-butyl 2-(4-(3-methyl-1,2,4-oxadiazol-5-yl)phenyl)morpholine-4-carboxylate (intermediate 18, 20.5 g, 86%).

Provenance & Evidence