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

Temperatur

80 °C

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.

1. temperaturecooled
2. filtrationfiltered through a pad of silica gel
3. washThe silica gel pad was washed with 1 L of a mixture of methanol:diethyl ether (5:1)
4. concentrationThe combined filtrates were concentrated in vacuo
5. temperatureto warm to 25° C. for 3 hours
6. customThe unreacted sodium hydride was quenched with water
7. additionThe mixture was diluted with dioxane (1.5 L) and diethyl ether (5 L)
8. filtrationfiltered through a plug of silica gel
9. washThe silica gel plug was then washed with ether
10. concentrationThe combined filtrates were concentrated
11. dissolutionthe residue was dissolved in dioxane (2 L)
12. temperaturecooled to 0° C.
13. stirringThe reaction mixture was stirred at 25° C. for 10 hours
14. temperaturethe mixture was refluxed for two hours
15. temperaturecooled
16. customevaporated
17. dissolutionThe residue was dissolved in isopropanol (2.5 L)
18. customThe precipitate that formed
19. filtrationwas filtered
20. washwashed with isopropanol (1 L)
21. customdried

ORD-Eintrag

ord-0ff9acb1bdfd43e9a18572ea9104b3bf

Quelldatensatz

uspto-grants-2013_02

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08367706B2