N-Methyl-2-piperidone → 5-methylaminopentanoic Acid

Participants

Reaction Conditions

Reaction Steps

1-methyl-2-piperidone (5 ml, 44.1 mmol) was combined with barium hydroxide (3.8 g, 26.95 mmol) and water (55 ml). The suspension was warmed to 110° C. for 6 hours then cooled over an ice bath. Gaseous carbon dioxide was bubbled through the solution for 20 minutes. The suspension was filtered through a celite pad and the filtrate was concentrated to dryness. The residue was triturated with acetonitrile, collected, rinsed with ether and dried in vacuo to yield 5-(methylamino)pentanoic acid as a white solid (2.95 g). 5-(Methylamino)pentanoic acid (5 g, 38 mmol), and Sodium hydroxide (50% aqueous solution, 6.6 g, 82 mmol) were suspended in water (30 ml) and dioxane (20 ml). Di-tert-butyl dicarbonate (11 g, 50 mmol) was added, then the mixture was stirred at room temperature for 16 hours. The mixture was diluted with water, acidified to approximately pH 5 with concentrated HCl and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, evaporated and dried in vacuo to give crude 5-[(tert-butoxycarbonyl)(methyl)amino]pentanoic acid as a thick clear oil (14 g).

Provenance & Evidence