Diisopropylamine → (6-((tert-butyldiphenylsilyloxy)methyl)-4-chloro-5-((2R,6S)-2,6-dimethylmorpholino)-3-fluoropyridin-2-yl)(1-methyl-1H-imidazol-2-yl)methanol

Participants

Reaction Conditions

Reaction Steps

Diisopropylamine (0.868 mL, 6.14 mmol) was added dropwise to a stirring solution of 2.5M butyllithium in hexanes (2.339 mL, 5.85 mmol) in THF (20 mL) at −78° C. The solution was warmed to 0° C. for 10 minutes and then cooled again to −78° C. Cannulation of the LDA at −78° C. into (2R,6S)-4-(2-((tert-butyldiphenylsilyloxy)methyl)-4-chloro-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine (Intermediate 45, 1.5 g, 2.92 mmol) in THF (10 mL) at −78° C. Allowed dark solution to stir for 20 minutes then cannulated into a stirring solution of 1-methyl-1H-imidazole-2-carbaldehyde (0.644 g, 5.85 mmol) in THF (10 mL) at −78° C. The solution was allowed to warm to −50° C. then quenched with saturated ammonium chloride solution. The mixture was extracted with ethyl acetate and washed resulting organics with brine. After drying the organics over sodium sulfate, filtering, and evacuating the filtrate under vacuum, a crude yellow oil was obtained. The crude oil was purified on silica using 40% ethyl acetate in n-hexane to give 1.2 g (66%) of the title compound as oil.

Provenance & Evidence