(NE,S)-2-methyl-N-[[4-[5-(trifluoromethyl)pyridin-2-yl]phenyl]methylidene]propane-2-sulfinamide → (S,S)-2-methyl-N-(3-methyl-1-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}butyl)propane-2-sulfinamide

Participants

Reaction Conditions

Reaction Steps

A three-neck three liter flask equipped with a mechanical stirred, internal thermometer, and dropping funnel was evacuated, heated with a heatgun, and backfilled with dry nitrogen three times. The apparatus was then charged with anhydrous zinc chloride (667 ml, 333 mmol, 0.5M in tetrahydrofuran) and the solution was cooled to 0° C. A solution of isobutylmagnesium bromide (511 ml, 1.02 mol, 2.0M in diethylether) was added dropwise to the well-stirred solution over approximately 1.5 hours, resulting in an exothermic reaction and the formation of a precipitate. The temperature was maintained below 15° C. through the course of the addition. At the conclusion, the dropping funnel was washed with tetrahydrofuran (3×20 ml) and the reaction was slowly warmed to ambient temperature and stirred for approximately 1.5 h. The reaction was cooled to −78° C., whereupon a solution of the (S)-2-methyl-N-[(1E)-{4-[5-(trifluoromethyl)pyridin-2-yl]phenyl}methylene]propane-2-sulfinamide (78.78 g, 222.3 mmol) in tetrahydrofuran (250 ml) was added dropwise over approximately 30 minutes. At this point, the reaction was quenched carefully with saturated aqueous ammonium chloride, the cold bath was removed, water was added and the reaction allowed to warm to ambient temperature. The contents were transferred to a separatory funnel, along with methyl tert-butylether and some additional water. The layers were separated and the aqueous layer was extracted with methyl tert-butylether (3×500 ml). The combined organic extracts were dried over magnesium sulfate, filtered, and concentrated in vacuo. The crude material was purified via ISCO MPLC (SiO2, 0-80% ethyl acetate in heptane) to yield the product (74.0 g, 81%) as a gum. 1H NMR (400 MHz, CDCl3, δ): 8.94 (s, 1H), 7.96-8.05 (m, 3H), 7.84 (d, J=8.2 Hz, 1H), 7.49 (d, J=8.2 Hz, 2H), 4.43-4.52 (m, 1H), 3.40-3.50 (m, 1H), 1.85-1.94 (m, 1H), 1.62-1.75 (m, 1H), 1.47-1.57 (m, 1H), 1.24 (s, 9H), 0.95 (d, J=6.4 Hz, 3H), 0.90 (d, J=6.6 Hz, 3H). MS (M-C4H10NOS): 292.1.

Provenance & Evidence