Processes for preparing (r)-2-methylpyrrolidine and (s)-2-methylpyrrolidine and tartrate salts thereof
a technology of methylpyrrolidine and s-methylpyrrolidine, which is applied in the field of processes for preparing s-methylpyrrolidine and s-methylpyrrolidine and tartrate salts thereof, can solve the problems of corrosive, time-consuming, expensive, and disadvantageous processes of previous development, and achieves the effects of reducing the number of steps
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example 1
Synthesis of (R)-2-methylpyrrolidine L-tartrate Using 5% Pt—C
[0900]2-Methylpyrroline (2.50 g, 30.12 mmol) was hydrogenated at 55 psi at ambient temperature for 16 hours in a mixture of 5% Pt—C (250 mg, catalytic), absolute ethanol (62 mL) and methanol (26 mL). Gas chromatographic analysis showed a 93.7% conversion of starting material to product. The mixture was filtered through Celite® (4 g) and the filtrate placed in a 250 mL, single-neck round bottom flask with stir bar along with L-tartaric acid (3.80 g, 25.32 mmol). The mixture was heated to 25° C. until a solution was obtained. Authentic (R)-2-methylpyrrolidine L-tartrate (10.0 mg) was added as seed crystals and the mixture stirred at ambient temperature for 16 hours. The mixture was cooled to 0° C. using an ice bath and was stirred for an additional 2 hours. Solids were filtered and then air-dried for 1 hour to provide (R)-2-methylpyrrolidine L-tartrate (3.55 g, 15.09 mmol, 50.1%). Chiral gas chromatographic analysis showed 5...
example 2
Synthesis of (R)-2-methylpyrrolidine L-tartrate Using Pt(IV) oxide
[0901]2-Methylpyrroline (2.50 g, 30.12 mmol) was hydrogenated at 55 psi at ambient temperature for 5 hours in a mixture of platinum (IV) oxide (250 mg, catalytic), absolute ethanol (62 mL) and methanol (26 mL). Gas chromatographic analysis showed a 98.3% conversion of starting material to product. The mixture was filtered through Celite® (4 g) and the filtrate placed in a 250 mL, single-neck round bottom flask with stir bar along with L-tartaric acid (3.80 g, 25.32 mmol). The mixture was heated to 25° C. until a solution was obtained. Authentic (R)-2-methylpyrrolidine L-tartrate (100.0 mg) was added as seed crystals and the mixture stirred at 25° C. for 8 hours. The mixture was allowed to cool to ambient temperature and was stirred an additional 16 hours. The mixture was cooled to 0° C. using an ice bath and was stirred for an additional 2 hours. Solids were filtered, washed with methanol (5 mL), and then air-dried fo...
example 3
Recrystallization of (R)-2-methylpyrrolidine L-tartrate
[0902]General Recrystallization Procedure: A portion of the product obtained in Example 1 (2.71 g) was placed in a 100 mL, single-neck round bottom flask with stir bar along with absolute ethanol (38 mL) and methanol (16 mL). The mixture was heated to 60° C. to form a solution and then allowed to cool to ambient temperature. Authentic (R)-2-methylpyrrolidine L-tartrate (2.50 mg) was added as seed crystals and the mixture was stirred at ambient temperature for 16 hours, and then at 0° C. (ice bath) for 2 more hours. Solids were filtered and dried at 60° C. in a vacuum oven with a stream of nitrogen at 29 in. Hg for 1 hour to provide (R)-2-methylpyrrolidine L-tartrate (1.80 g, 66.4% recovery). Chiral gas chromatographic analysis showed 84.9% ee, 93% overall purity.
[0903]The obtained solids (1.79 g) were further resolved according to the General Recrystallization Procedure using 25 mL absolute ethanol and 11 mL methanol to provide ...
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