3-Azetidinecarbonitrile synthesis

Yield:-

Reaction Conditions:

with hydrogenchloride in 1,4-dioxane;water; for 2 h;

Steps:

12

To a solution of l-N-Boc-3-cyanoazetidine (5.0 g, 27.5 mmol) in 1,4- dioxane (50 mL) was added 4 N HCl (50 mL) and stirred for 2 h. The reaction was concentrated under vacuum. The residue was dissolved in CH₂Cl₂ (60 mL) and DIPEA (10.6 mL, 60.4 mmol) and added l-methylimidazole-4-sulfonyl chloride (4.94 g, 27.5 mmol) and stirred at room temperature for 20 h. The reaction mixture was washed with 2 N NaOH (50 mL), dried over MgSO₄ and concentrated under vacuum to afford 8 as a white crystalline solid (4.97 g, 80%); ; Η-nmr (300 MHz, CDCl₃) δ 7.06 (s, IH), 7.56 (s, IH), 4.27-4.19 (m, 4H), 3.82 (s, 3H), 3.43-3.31 (m, IH); LC-MS (214) 99%, 0.93 min, m/z 227 '.1 (M+H).

References:

WO2010/114907,2010,A1 Location in patent:Page/Page column 91