Methanol → (S)-2-methyl-1-phenyl-2-(pyridine-2-yl)propan-1-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of (R)-2-methyl-N—((S)-2-methyl-1-phenyl-2-(pyridin-2-yl)propyl)propane-2-sulfinamide (1200 g, 3.631 moles) dissolved in dichloromethane (12000 mL) was added 4N hydrogen chloride/dioxane solution (3000 mL, 12.00 moles) in a steady stream over a period of 1 hour at room temperature. A thick suspension formed, which was continued stirring for 1.5 hours at 32° C.; at which point Methanol (1000 mL) was added to improve stirring. After 30 minutes additional stirring, all of the solids dissolved, giving a clear amber solution and indicating complete reaction. The solvents were removed under reduced pressure leaving a gummy amber residue. The residue was taken up in distilled water (5000 mL), and the resulting solution washed with diethyl ether (2×1000 mL) to remove neutral impurities. The acidic solution was treated with solid Sodium hydroxide (400 g, 10.00 moles) until strongly basic (pH=11). The resulting aqueous mixture was extracted with dichloromethane (2×1000 mL, then 2×500 mL). The combined organic extracts were dried (anhydrous magnesium sulfate). Filtration, followed by removal of the solvent under reduced pressure, left a thick amber syrup. This residue was further dried under high vacuum to yield the crude de-protected amine (880.9 g, 107.2% of theory). 1H NMR (300 MHz, CHLOROFORM-d) δ ppm 8.64 (d, J=3.79 Hz, 1H) 7.57 (td, J=7.69, 1.90 Hz, 1H) 7.05-7.30 (m, 7H) 4.48 (s, 1H) 1.47 (br.s., 2H) 1.36 (s, 3H) 1.25 (s, 3H). MS: m/z 227.

Provenance & Evidence