6-(cyclohexyloxy)-3-Pyridinecarbonitrile synthesis

Yield:928648-56-0 71%

Reaction Conditions:

Stage #1: cyclohexanolwith sodium hexamethyldisilazane in tetrahydrofuran at 20; for 0.5 h;
Stage #2: 6-chloronicotinonitrile in tetrahydrofuran at 20;

Steps:

25

Preparation 25; S-Aminomethyl-θ-cyclohexyloxy-pyridine; θ-Cyclohexyloxy-pyridine-S-carbonitrile; Add sodium bis(trimethylsilyl)amide (3.9 mL, 7.93 mmol, 2M solution in THF) to a solution of cyclohexanol (824 μL, 7.93 mmol) in THF (10 mL). Stir for 30 min at room temperature and then add a solution of 6-chloro- nicotinonitrile (1 g, 7.2 mmol) in anhydrous THF (5 mL). Stir at room temperature overnight and then quench the reaction by addition of saturated aqueous NaHCO₃ (100 mL) and extract the aqueous phase with DCM (3x100 mL). Wash the combined organic extracts with brine (100 mL), dry over MgSO₄ and concentrate in vacuo to obtain the desired intermediate as a yellow solid (1.04 g, 71%).

References:

WO2007/28083,2007,A2 Location in patent:Page/Page column 76