tert-butyl 4-(chloromethyl)piperidine-1-carboxylate synthesis

Yield:479057-79-9 100%

Reaction Conditions:

with tetrachloromethane in dichloromethane at 20;

Steps:

6.a

A suspension of PS-triphenylphosphine resin (3.20 g, 6.69 mmol at 2.20 mmol/g, Argonaut Technologies) in 25 mL of anhydrous dichloromethane was treated with CCI₄ (0.670 mL, 6.96 mmol). After stirring at RT for 30 minutes, a solution of f-butyl 4-(hydroxymethyl)-1-piperidinecarboxylate (0.500 g, 2.32 mmol, Aldrich) in 5 mL of dichloromethane was added. After stirring the mixture at RT overnight the resin was removed by vacuum filtration. The resin was washed with dichloromethane (2x)followed by MeOH (2x). The filtrate was concentrated to dryness at reduced pressure to afford 0.54 g (100%) off-butyl 4-(chloromethyl)-1-piperidinecarboxylate as a white, crystalline solid. ¹H NMR (DMSO-cfe): 5 3.91 (d, 2H), 3.51 (d, 2H), 2.77-2.55 (brs, 2H), 1.80-1.62 (m, 3H), 1.36 (s, 9H), 1.06 (m, 1H).

References:

WO2006/20415,2006,A1 Location in patent:Page/Page column 61; 62