Hexachloroethane → (2R,6S)-4-(2-((tert-Butyldiphenylsilyloxy)methyl)-4-chloro-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine

Participants

Reaction Conditions

Reaction Steps

A solution of diisopropylamine (3.51 ml, 24.65 mmol) in THF (30 ml) was cooled in a dry ice-acetone bath. A solution of n-butyllithium (2.5 M in hexanes, 9.28 ml, 23.20 mmol) was added and the mixture was warmed to 0° C. and recooled in a dry ice-acetone bath. The solution was added to a second solution of (2R,6S)-4-(2-((tert-butyldiphenylsilyloxy)methyl)-5-fluoropyridin-3-yl)-2,6-dimethylmorpholine (Intermediate 44, 6.94 g, 14.50 mmol) in THF (30 ml) cooled in a dry ice-acetone bath. The mixture was stirred for 45 minutes before the solution was transferred via cannula to a solution of hexachloroethane (2.79 ml, 24.65 mmol) in 60 ml THF also cooled in a dry ice-acetone bath. The mixture was allowed to warm to room temperature before being diluted with EtOAc and washed with water and brine. The combined aqueous layers were extracted again with EtOAc, which was washed with brine. Drying (MgSO4) of the combined EtOAc extracts and removal of solvent gave a gummy solid that was chromatographed on silica gel (50% hexanes in CH2Cl2 followed by gradient elution to 100% CH2Cl2) to afford product as an oil that slowly solidified (5.26 g yield). MS (ES) MH+: 513 for C28H34ClFN2O2Si.

Provenance & Evidence