Oxalyl chloride → Ethyl 1-(5-bromopyrimidine-2-carbonyl)-4-methylpiperidine-4-carboxylate

Participants

Reaction Steps

To a solution of 5-bromopyrimidine-2-carboxylic acid (0.150 g, 0.742 mmol) and DMF (1 drop, catalytic amount) in DCM (10 mL) was added dropwise oxalyl chloride (0.10 mL, 1.11 mmol.) at 0° C. under inert atmosphere and the mixture stirred at rt for 1 h. The solvent was evaporated under reduced pressure under an inert atmosphere and the residue taken up in THF (5 mL) followed by the addition of DIPEA (0.70 mL, 3.71 mmol) and ethyl 4-methylpiperidine-4-carboxylate hydrochloride (0.14 g, 0.89 mmol.) at 0° C. The resulting mixture was stirred at rt for 16 h. After completion of reaction (by TLC) the mixture was poured into ice cold water (100 mL), extracted with EtOAc (3×100 mL) and the combined organics washed with water and brine, dried over Na2SO4 and filtered. The solvent was evaporated under reduced pressure and the crude residue purified on silica-gel eluting with 40% EtOAc in hexane to obtain the desired product as an off white semi-solid (0.10 g, 37% yield). MS: 358.01 [M+H]+.

Provenance & Evidence