(R)-3-Methylmorpholine → (6S)-8-benzyl-6-methyl-3-[(3R)-3-methylmorpholin-4-yl]-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine

Participants

Reaction Conditions

Reaction Steps

A suspension of (6S)-8-benzyl-3-chloro-6-methyl-6,7,8,9-tetrahydropyrazino[2,3-f][1,4]oxazepine (313 mg), (3R)-3-methylmorpholine (164 mg), Pd2(dba)3 (30 mg), XPhos (62 mg) and sodium tert-butoxide (208 mg) in toluene (5 mL) was stirred under an argon atmosphere with heating at 100° C. for 3 hr. Water was added to the reaction mixture, the aqueous layer was extracted with ethyl acetate, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (solvent gradient: 9→50% ethyl acetate/hexane) to give the title compound (233 mg, 61%) as a pale-yellow oil.

Provenance & Evidence