2-Methylsulfanylpyrimidine-4-carbaldehyde → (5-((tert-butyldiphenylsilyloxy)methyl)-4-((2R,6R)-2,6-dimethylmorpholino)-2,3-difluorophenyl)(2-(methylthio)pyrimidin-4-yl)methanol

Participants

Reaction Steps

Starting materials: (2R,6R)-4-(6-((tert-butyldiphenylsilyloxy)methyl)-2,3-difluorophenyl)-2,6-dimethylmorpholine (Intermediate 43, 7.36 g, 14.84 mmol) in t-BuOMe (20 mL) was added s-BuLi (12.45 mL, 16.19 mmol) at −75° C. under nitrogen atmosphere. After stirring for 20 minutes at this temperature, it was then transferred via cannula to a solution of 2-(methylthio)pyrimidine-4-carbaldehyde (2.08 g, 13.49 mmol) in t-BuOMe (20 mL) (precooled down to −70° C.), the mixture was then stirred for 0.5 hour at −70° C., quenched with saturated aqueouse ammonium chloride solution and extracted with ethylacetate, dried and concentrated, purified by flash column chromatography on silica gel with Hex/EtOAc to give the desired product (3.024 g).

Provenance & Evidence