4-(5-(Trifluoromethyl)pyridin-2-yl)benzaldehyde → (NE,S)-2-methyl-N-[[4-[5-(trifluoromethyl)pyridin-2-yl]phenyl]methylidene]propane-2-sulfinamide

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Reaction Steps

A three-neck two liter flask equipped with dropping funnel, reflux condenser, and mechanical stirrer was charged with 4-[5-(trifluoromethyl)pyridin-2-yl]benzaldehyde (69.00 g, 274.7 mmol) and (S)-(−)-2-methyl-2-propanesulfinamide (33.66 g, 277.7 mmol). The apparatus was purged with dry nitrogen and warmed with a heat gun. The solids were suspended in dichloromethane (1.0 L) whereupon titanium(IV) ethoxide (115 ml, 549 mmol) was added dropwise over 30 minutes during which time the solids dissolved affording a yellow solution. No increase in temperature was observed. The reaction was heated to reflux for 12 hours. The reaction was quenched with a dropwise addition of MeOH (400 mL) followed by saturated aqueous sodium bicarbonate (150 mL). The resulting precipitate was removed by filtration through a pad of 1:1 celite:florisil and the filter cake was washed with ethyl acetate (3×200 ml). The resulting mixture was partially concentrated under vacuum (50% volume) and then dried over magnesium sulfate. The resulting solution was filtered through a Buchner funnel, the salts were washed with ethyl acetate (3×200 ml) and the resulting filtrate was concentrated in vacuo. The crude solid was suspended in heptane (250 ml) and heated to boiling with a heat gun whereupon ethyl acetate was added in aliquots to dissolve the solids. The mixture was then cooled slowly to affect crystallization (slowly to ambient temperature, then with ice). The solids were collected by vacuum filtration, and the process was repeated once more to yield the final product (78.78 g, 81%) as an off-white crystalline solid. 1H NMR (400 MHz, CDCl3, δ): 9.01 (s, 1H), 8.67 (s, 1H), 8.19 (d, J=8.4 Hz, 2H), 8.07 (dd, J=8.4, 2.0 Hz, 1H), 8.01 (d, J=8.4 Hz, 2H), 7.94 (d, J=8.2 Hz, 1H), 1.30 (s, 9H). MS (M+1) 355.1.

Provenance & Evidence