Ammonia → 5-(Aminomethyl)-1-methylpyrrolidin-2-one

Participants

Reaction Conditions

Reaction Steps

A mixture of (1-methyl-5-oxopyrrolidin-2-yl)methyl 4-methylbenzenesulfonate (196 g, 0.73 mol), sodium azide (142 g, 2.19 mol) and N-methyl-2-pyrrolidinone (800 ml) was heated to 80° C. for two hours, cooled, diluted with diethyl ether (3 L) and filtered through a pad of silica gel. The silica gel pad was washed with 1 L of a mixture of methanol:diethyl ether (5:1). The combined filtrates were concentrated in vacuo. The residue was subsequently treated with a suspension of sodium hydride in mineral oil (60%, 44 g, 1.1 mol) at 10-15° C. under rapid stirring for two hours followed by the addition of lithium iodide (155 g, 1.1 mol). The reaction mixture was allowed to warm to 25° C. for 3 hours. The unreacted sodium hydride was quenched with water. The mixture was diluted with dioxane (1.5 L) and diethyl ether (5 L) and filtered through a plug of silica gel. The silica gel plug was then washed with ether. The combined filtrates were concentrated, the residue was dissolved in dioxane (2 L), cooled to 0° C., and triphenylphosphine (191 g, 0.73 mol) was added at 0° C. for 1 hour. The reaction mixture was stirred at 25° C. for 10 hours, then water (25 mL) and aqueous ammonia (1 mL, 25%) were added, and the mixture was refluxed for two hours, cooled, and evaporated. The residue was dissolved in isopropanol (2.5 L), and to the solution was added a solution of oxalic acid (88 g, 0.7 mol) in isopropanol (1 L). The precipitate that formed was filtered, washed with isopropanol (1 L), and dried to give the title compound as the oxalate salt.

Provenance & Evidence