Synthesis
The amine solution (145 g) was dissolved in THF (200 mL) and added dropwise to a cooled solution of potassium tert-butanolate (58.9 g) in THF (500 mL) over 1 hour. The mixture was stirred at 0C for 2.5 hours and then warmed to room temperature over 1 hour with stirring. An additional 50 mL of 1.0 M potassium tert-butanol in THF was added, and after 1 h, the solvent was removed under vacuum and the residue was dissolved in ethyl acetate (1 L). The organic solution was washed with saturated ammonium chloride (2 x 500 mL) and back-extracted with ethyl acetate (2 x 500 mL). The organic extracts were combined, dried with anhydrous magnesium sulfate, filtered and concentrated in vacuum to give 120.6 g of the crude product, 2-methyl-4-piperidone, as an oil. The oily substance was then treated with 5NHCl (700 mL) at reflux for about 14.5 hours. After cooling, the solution was washed with a mixture of ethyl acetate/ether (1:1, 2 x 300 mL). The aqueous layer was then concentrated to give 2-methyl-4-piperidone hydrochloride.
