tert-Butyl acrylate → (E)-3-(6-Amino-5-piperidin-1-ylmethyl-pyridin-3-yl)acrylic acid tert-butyl ester

Participants

Reaction Steps

A solution of 5-bromo-3-piperidin-1-ylmethyl-pyridin-2-ylamine (500 mg, 1.85 mmol), tert-butyl acrylate (0.3 mL, 2.0 mmol), (i-Pr)2EtN (0.5 mL, 2.8 mmol) and P(o-tol)3 (114 mg, 0.37 mmol) in EtCN (10 mL) was de-oxygenated with argon for 30 min. Pd(OAc)2 (43 mg, 0.19 mmol) was added, and the mixture was de-oxygenated for 15 min. The mixture was heated to reflux for 18 h and then allowed to cool. The solvent was removed in vacuo. The residue was partitioned between EtOAc and H2O. The organic layer was washed with H2O and satd NaCl, dried over Na2SO4 and concentrated. Purification by column chromatography (silica gel, CH2Cl2 to 96:4 CH2Cl2/CH3OH) gave the title compound (350 mg, 60%) as a yellow solid: MS (ESI) m/e 318 (M+H)+.

Provenance & Evidence