Benzophenone imine → (R)-5-[5-(benzhydrylidene-amino)-2-fluoro-phenyl]-5-methyl-morpholin-3-one

Participants

Reaction Conditions

Reaction Steps

Under a nitrogen atmosphere a solution of (R)-5-(5-bromo-2-fluoro-phenyl)-5-methyl-morpholin-3-one (building block B) (1.2 g, 4.17 mmol) in toluene (20 ml) was treated with benzophenonimine (1.59 g, 8.33 mmol), tris(dibenzylideneacetone)-dipalladium chloroform complex (133 mg, 0.125 mmol), tert-butyl X-phos (182 mg, 0.417 mmol) and sodium tert-butoxide (1.24 g, 12.5 mmol). The mixture was stirred in a sealed tube at 105° C. for 18 hours. For the workup, the brown reaction mixture was evaporated and the residue directly purified by flash chromatography on a silica-amine phase using a gradient of heptane/ethyl acetate=100:0 to 40:60 as the eluent. The (R)-5-[5-(benzhydrylidene-amino)-2-fluoro-phenyl]-5-methyl-morpholin-3-one was obtained as a yellow solid (1.53 g, 95%); (calculated) C24H21FN2O2 [388.45]; (found) [M+H]+=389.

Provenance & Evidence