2-Methylpyridine → 3-(2-((S)-1-((S)-1,1-dimethylethylsulfinamido)-2-(pyridin-2-yl)ethyl)phenyl)benzo[d]isoxazole-6-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-picoline (22.6 mL, 21.3 g) in tetrahydrofuran (280 mL) cooled under nitrogen to −72° C. was added a 2.5M in hexanes solution of n-butyl lithium (98 mL) dropwise over 40 min keeping the internal temperature less than −70° C. The mixture was stirred at this temp for 45 min then a solution of 3-(2-((E)-((S)-tert-butylsulfinylimino)methyl)phenyl)benzo[d]isoxazole-6-carboxamide (Compound 10) (28.2 g) in tetrahydrofuran (280 mL) was added dropwise over 45 min (the internal temperature less than −70° C.) then stirred at this temp for 30 min. Reaction mixture allowed to warm to −30° C. and saturated aqueous ammonium chloride (500 mL) added. The layers were separated and aqueous layer washed with ether (3×300 mL). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and the solvents removed. Flash chromatography on silica eluting with ethyl acetate then 1 to 5% methanol in ethyl acetate gave three fractions of product that were crystallised from the minimum of ethyl acetate to give the title product (17.2 g).

Provenance & Evidence