Methanamine, hydrochloride (1:1) → 1-[4-(Methylamino)piperidin-1-yl]ethan-1-one--hydrogen chloride (1/1)

Participants

Reaction Steps

Potassium hydroxide flakes (2 g) were added to a solution of methylammonium chloride (8.5 g) in methanol (75 ml) at 0°-5°. 1-Acetylpiperid-4-one (14 g) was then added, the mixture stirred for 15 minutes and then a solution of sodium cyanoborohydride (2.5 g) in methanol (25 ml) was added over a period of 30 minutes. The mixture was stirred at room temperature overnight and then potassium hydroxide (6 g) was added. After filtration through sodium carbonate, the filtrate was evaporated to dryness and the residue was partitioned between chloroform (100 ml) and aqueous potassium hydroxide (2.5 g in 15 ml H2O). The chloroform layer was dried (Na2CO3) and evaporated to give a colorless oil which was dissolved in a mixture of ethanol (40 ml) and isopropyl alcohol (40 ml), then excess hydrogen chloride gas was bubbled into the cooled solution (ice bath). Addition of acetone resulted in the slow crystallization of 1-acetyl-4-methylaminopiperidine hydrochloride (5.5 g) (identified by n.m.r.).

Provenance & Evidence