AZETIDINE-3-CARBONITRILE HYDROCHLORIDE synthesis

Yield:345954-83-8 195 g

Reaction Conditions:

with hydrogenchloride in 1,4-dioxane at 0 - 20; for 4 h;

Steps:

3.1 Step 1:
Step 1:
Preparation of azetidine-3-carbonitrile Hydrochloride
To a solution of tert-butyl 3-cyanoazetidine-1-carboxylate (300 g, 1.65 mol, Pharma Blocks) in 1,4-dioxane (300 mL) at 0° C. was added 4M HCl in dioxane (1.25 L, 5.0 mol).
The mixture was allowed to warm to rt and stirred for an additional 4 h.
The reaction mixture was then concentrated under reduced pressure and azeotroped with toluene (3*250 mL).
The residue was slurried with hexanes (500 mL) and dried under high vacuum to give azetidine-3-carbonitrile hydrochloride (195 g) as a white solid. ¹H NMR (400 MHz, DMSO-d₆): δ 9.87 (bs, 2H), 4.22-4.08 (m, 4H), 4.05-3.95 (m, 1H).

References:

AMGEN INC.;CYTOKINETICS, INC.;Ashcraft, Luke;Boezio, Alessandro;Butler, John;Chandra, Aroop;Chuang, Chihyuan;Collibee, Scott E.;Debenedetto, Mikkel;DiMassa, Vincent;Graceffa, Russell;Malinowski, Justin;Moebius, David;Morgan, Bradley P.;Payette, Joshua;Romero, Antonio;St. Jean, JR., David;Vargas, Richard;Yeoman, John;Zhang, Hanmo US2019/77793, 2019, A1 Location in patent:Paragraph 0204