Tetrahydrofuran → N-(2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine tartrate hemihydrate

Participants

Reaction Steps

To a solution of N-(2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine (193.6 g, 0.6 mol) in 2 L THF at 65° C. are added seed crystals and L-tartaric acid (90.15 g, 0.6 mol, 1 equiv.) solution in 100 ml water dropwise over 5 min (after 15 min the solution becomes turbid and the product begins to crystallize). After 3 h at 64° C., the mixture is cooled down to room temperature, and then stirred for an additional 20 h. The reaction mixture is then cooled down to 10° C. and filtered; the solid is washed with cold THF/water 95/5 and dried under vacuum to afford 245.8 g of N-(2-methylpropyl)-N-[(2,4-dichloro-1,3-thiazol-5-yl)methyl]piperidin-4-amine tartrate hemihydrate (87% yield). 1H NMR (250 MHz, DMSO d6): δ=3.97 (2H, s), 3.69 (2H, s), 3.24 (2H, brd), 2.77 (3H, m), 2.20 (2H, d), 1.63 (5H, m), 0.80 (6H, d); 13C NMR (62 MHz, DMSO d6): δ=175.09, 149.48, 138.32, 131.24, 72.39, 58.12, 55.08, 47.04, 43.29, 26.72, 24.60, 20.81.

Provenance & Evidence