Potassium Carbonate → Tert-butyl 4-(pyridin-4-ylmethyl)piperidine-1-carboxylate

Participants

Reaction Steps

9-borabicyclo[3.3.1]nonane (101.5 ml of a 0.5M solution in tetrahydrofuran) was added to a degassed sample of N-(tert-butoxycarbonyl)-4-methylene piperidine (may be prepared as described in A. Palani et al., J. Med. Chem., 2002, 45: 3145) (10 g) and the resultant solution heated at reflux for 1 h. After cooling to room temperature the reaction mixture was then added to a mixture of 4-bromopyridine (7.23 g), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (1.14 g), K2CO3 (8.42 g), N,N-dimethylformamide (100 ml) and water (10 ml), and the resultant mixture heated at 60° C. for 3 h. After cooling to room temperature, another charge of [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (1.14 g) was added to the reaction and heated at 60° C. overnight. The mixture was cooled to room temperature and poured into water, the pH was adjusted to 11 by the addition of 10% aqueous sodium hydroxide and extracted into ethyl acetate. Combined organic extracts were dried (Na2SO4) and evaporated to give the crude pyridine as a brown viscous oil. Chromatography [silica gel, eluting with ethyl acetate in hexanes, 0-100%] gave the title compound (D1) as a pale yellow oil (7.5 g).

Provenance & Evidence