4-Hydrazinyl-1-piperidinecarboxylic acid 1,1-dimethylethyl ester hydrochloride synthesis

Yield: 59%

Reaction Conditions:

with hydrazine hydrochloride;hydrogen;platinum on carbon in methanol;water under 45603.1 Torr; for 15 h;Inert atmosphere;Sealed autoclave;

Steps:

11
Preparation 11 : te/t-Butyl 4-hvdrazinopiperidine-i-carboxylate hydrochloride saltInto a solution of te/t-butyl 4-oxopiperidine-1-carboxylate (50 g, 0.25 mmol) in methanol (500 ml.) in an autoclave was added hydrazine mono-hydrochloride (17.2 g, 0.25 mmol) in water (100 ml_). The white mixture was stirred under argon followed by the addition of 5% platinum on carbon (750 mg) as a slurry in water. The autoclave was sealed and charged to 60 atmospheres with hydrogen, and the reaction was stirred for 15 hours. Upon completion, the reaction was filtered through Celite, and the pad washed with methanol. This preparation was carried out six times. The combined filtrates were concentrated under reduced pressure, and the resulting white precipitate (di-te/t-butyl- 4,4'-hydrazine-1 ,2-diyldipiperidine-1-carboxylate) by-product was collected by filtration and washed several times with water. The aqueous filtrate was then concentrated under reduced pressure to give the desired product (221 g, 59%) as a colorless solid. ¹H NMR (400MHz, deuterochloroform) delta 4.13 (br s, 2H), 3.32 (br t, 1 H), 2.77 (br t, 2H), 2.16 (m, 2H), 1.66 (m, 2H), 1.43 (s, 9H).

References:

PFIZER INC.;MASCITTI, Vincent;MCCLURE, Kim Francis;MUNCHHOF, Michael John;ROBINSON, Jr., Ralph Pelton WO2010/140092, 2010, A1 Location in patent:Page/Page column 54