Methane → (s)-2-Methyl-1-phenyl-2-(pyridine-2-yl)propan-1-amine fumarate salt

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Reaction Steps

(S)-2-methyl-1-phenyl-2-(pyridine-2-yl)propan-1-amine (821.7 g, 3.63 moles) was dissolved in methanol (5000 mL) giving a reddish-orange solution. The solution was treated with Norit decolorizing Carbon (50 g) and stirred at gentle reflux for 2 hours. The hot solution was filtered through a pad of Celite, giving a light yellow filtrate. The Carbon filter cake was further washed with hot methanol (2×1000 mL), and the washes combined with the original filtrate. The decolorized solution of (4) was treated with fumaric acid (421.4 g, 3.63 moles), added as a dry solid over a period of 5 minutes. The solution was allowed to stir at room temperature for 30 minutes, then was concentrated under reduced pressure to remove most of the methanol (6000 mL removed). The resulting thick amber syrup was diluted gradually with vigorous stirring with diethyl ether (7000 mL) until crystallization ensued. The mixture was stirred vigorously until a very healthy crop of crystals had formed. The mixture was then further diluted with additional diethyl ether (2000 mL, total volume of 9000 mL) with vigorous stirring to complete the crystallization. The crystals were collected by suction filtration and pulled free of liquors. The crystals were re-suspended in a mixture of 9:1 diethyl ether/methanol (2000 mL) and stirred vigorously for several minutes, then re-filtered and pulled dry. The process was repeated a second time. The white crystals obtained from this treatment were dried to constant weight in the vacuum oven at 60° C. to yield (S)-2-methyl-1-phenyl-2-(pyridine-2-yl)propan-1-amine fumarate salt (1179.3 g, 95% yield). 1H NMR (300 MHz, DMSO-d 6) δ ppm 9.19 (br. s., 3 H) 8.62 (d, J=3.37 Hz, 1 H) 7.71 (td, J=7.80, 1.69 Hz, 1 H) 7.17-7.39 (m, 5 H) 6.94-7.17 (m, 2 H) 6.51 (s, 2 H) 4.64 (s, 1 H) 1.35 (s, 3 H) 1.26 (s, 3 H). 13C NMR (75 MHz, DMSO-d 6): δ ppm 23.7, 25.7, 43.8, 62.7, 121.3, 122.3, 128.0, 128.1, 128.6, 135.5, 137.4, 137.8, 148.7, 164.9, 168.3. MS: m/z 227.

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