Methylamine → 1-Methoxy-4-methylamino-piperidine-4-carbonitrile

To a solution of 1-methoxy-piperidin-4-one [prepared according to Journal of Organic Chemistry (1961), 26, 1867-74] (100 g, 0.77 mol), aqueous methylamine (40 wt. % in H2O, 86 ml) and methylamine hydrochloride (57.5 g, 0.85 mol) in water (700 ml) at 0° C. was added a solution of potassium cyanide (55.5 g, 0.85 mol) in water (150 ml) dropwise over one hour. The reaction mixture was stirred at room temperature for two days. Over the next five days, the mixture was further treated with methylamine hydrochloride (5×2.6 g, total 13.0 g), aqueous methylamine (5×4.3 ml, total 21.5 ml) and potassium cyanide (5×2.5 g, total 12.5 g), and stirring continued at room temperature until the reaction was judged complete by thin layer chromatography. The aqueous reaction mixture was extracted with dichloromethane (lx 500 ml, and 4×200 ml), the combined organic phases dried over sodium sulfate and evaporated. Yield: 113.0 g of 1-methoxy-4-methylamino-piperidine-4-carbonitrile (compound P5.1) as a red liquid. This material was used without further purification in the next step.

1. stirringstirring
2. customcontinued at room temperature until the reaction
3. extractionThe aqueous reaction mixture was extracted with dichloromethane (lx 500 ml, and 4×200 ml)
4. dry with materialthe combined organic phases dried over sodium sulfate
5. customevaporated
6. customThis material was used without further purification in the next step

ORD-Eintrag

ord-9e00754f24fb481881dac6898bab097d

Quelldatensatz

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09018135B2