1-Benzylpiperidine-4-carbonitrile hydrochloride synthesis

Yield:1082951-20-9 88%

Reaction Conditions:

Stage #1: 4-cyanopiperidine;benzaldehydewith sodium tris(acetoxy)borohydride;acetic acid in tetrahydrofuran;
Stage #2: with water;sodium hydrogencarbonate in tetrahydrofuran;ethyl acetate;
Stage #3: with hydrogenchloride in diethyl ether at 0;

Steps:

48

Preparation 48; Add 4-Cyanopiperidine (7.19 g; 1.00 equiv; 65.269 mmoles); benzaldehyde (1.05 equiv; 68.533 mmoles; 7.0 mL), then sodium triacetoxyborohydride (1.3 eq, 84.85 mmoles; 18.73 g) to 2%(v/v) acetic acid in tetrahydrofuran (435 mL) and stir rapidly until complete. Dilute with ethyl acetate and wash with sat. sodium bicarbonate, saturated aqueous sodium chloride , dry with MgSO₄, filter, evaporate under reduced pressure to give 13.0 g oil. Dissolve in ether (-300 mL), filter, and slowly add 60 mL IM HCl in ether. Cool in ice bath. Filter, rinse with ether, dry under vacuum and collect 13.616 g (57.51 mmol, 88%) l-benzyl-piperidine-4-carbonitrile. MS (ES): m/z = 201 [M + H].

References:

WO2008/140947,2008,A1 Location in patent:Page/Page column 26