4-Methylmorpholine → Ammonium Hydroxide

Participants

Reaction Steps

3,6-Dihydro-N-methyl-4-(1-naphthalenyl)-1-(2H)-pyridinepropanamine (2.05 g, 7.30 mmol), 2,4-dichloropyridine (1.08 g, 7.30 mmol), and 4-methylmorpholine (10 mL) were heated in a Parr bomb at 140° C. for 72 h. Upon cooling to room temperature the crude mixture was diluted with chloroform (700 mL) and washed with 100 mL portions of aqueous 10% potassium carbonate and saturated aqueous sodium chloride. The organic layer was dried over anhydrous magnesium sulfate, filtered, and concentrated. Silica gel chromatography (50:50:1 toluene:EtOAc:NH4OH) of the concentrate afforded 3,6-dihydro-N-methyl-N-(4-chloro-2-pyridinyl)-4-(1- naphthalenyl)-1(2H)-pyridinepropanamine (A) (244 mg) and 3,6-dihydro-N-methyl-N-(2-chloro-4-pyridinyl)-4-(1-naphthalenyl)-1(2H)-pyridinepropanamine B) (190 mg). The fumarate salts were made by dissolving the free bases (232 mg (A), 0.59 mmol; 200 mg (B), 0.51 mmol) along with fumaric (137 mg, 1.18 mmol; 188 mg, 1.02 mmol respectively) in a solution of hot EtOAc (10 mL) followed by the addition of minimal amounts of MeOH. Upon cooling to room temperature overnight the resultant crystals (128 mg, 41% yield of A; 148 mg, 56% yield of B) were collected by filtration and dried at 65° C. under vacuum (0.05 mm Hg) for 20 h.

Provenance & Evidence