Uses
2-Methoxy-2-methylpropan-1-amine is a useful research chemical used in the preparation of diaryl dihydropyrazolo[3,4-c]pyridinones and dihydropyrazolo[3,4-f][1,4]oxazepinones as bicyclic lactam-based cannabinoid-1 receptor antagonists for the treatment of obesity.
Synthesis
Example 3 Synthesis of 2-methoxy-2-methylpropylamine: phthalimide potassium salt (3.70 g, 20 mmol) was added to a solution of 1-bromo-2-methoxy-2-methylpropane (3.34 g, 20 mmol) dissolved in 100 mL of dimethylformamide. The reaction mixture was refluxed with stirring for 4 hours, followed by slow cooling to 25°C. After adding 200 mL of chloroform, the mixture was poured into 500 mL of cold water. The aqueous phase was separated and extracted with two 50 mL chloroform. The combined chloroform extracts were washed sequentially with 100 mL of 0.2 N sodium hydroxide solution and 100 mL of water. After drying, the chloroform was removed under reduced pressure. The residue was dissolved in 100 mL of methanol, hydrazine hydrate (2 g, 40 mmol) was added and heated at reflux for 1 hour. After completion of the reaction, methanol was removed by concentration under reduced pressure. Concentrated hydrochloric acid was added to the residual aqueous solution and heated at reflux for 1 hour. Subsequently, it was concentrated under reduced pressure to remove most of the hydrochloric acid. The pH of the wet residue was adjusted to 14 with sodium hydroxide solution and poured into a separatory funnel containing a saturated potassium carbonate solution. The resulting solution was distilled at atmospheric pressure and the product 2-methoxy-2-methylpropylamine (1.6 g, 78% yield) was collected at 125 °C. The product was characterized by infrared spectroscopy (neat) and the major absorption peaks were located at 3280, 3065, 2960, 2920, 1640, 1430, 1365, 1075 cm1.
