tert-Butyl (1-(cyanomethyl)piperidin-4-yl)carbamate synthesis

Yield:259180-66-0 48%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in N,N-dimethyl-formamide at 65; for 12 h;

Steps:

tert-Butyl (1-(cyanomethyl)piperidin-4-yl)carbamate (47)

To a solution of 4-Boc-aminopiperidine 46 (100 mg, 0.500 mmol) in DMF (5.00 mL) was added 2-bromoacetonitrile (111 mL, 1.65 mmol) and DIPEA (428 mL, 2.50 mmol) at room temperature. After the mixture was stirred at 65 °C for 12 h, the mixture was added saturated NaHCO₃ aq. and extracted with CHCl₃. The organic layer was dried over MgSO₄, then concentrated under reduced pressure, followed by silica gel column chromatography (CHCl₃ to CHCl₃/CH₃OH = 10:1) to provide the title compound 47 (57.2 mg, 48%) as white powder. ¹H-NMR (500 MHz, CDCl₃) d 1.44-1.54 (m, 11H), 1.99-2.01 (m, 2H), 2.44-2.53 (m, 2H), 2.78-2.80 (m, 2H), 3.52 (s, 2H), 4.45-4.46 (m, 1H); HRMS (ESI), m/z calcd for C₁₂H₂₂N₃O₂⁺ [M+H]⁺ 240.1707, found 240.1705.

References:

Tsuji, Kohei;Kobayakawa, Takuya;Konno, Kiju;Masuda, Ami;Takahashi, Kohei;Ohashi, Nami;Yoshimura, Kazuhisa;Kuwata, Takeo;Matsushita, Shuzo;Harada, Shigeyoshi;Tamamura, Hirokazu [Bioorganic and Medicinal Chemistry,2022,vol. 56,art. no. 116616] Location in patent:supporting information