METHYL 1-(5-BROMOPYRIMIDIN-2-YL)PIPERIDINE-4-CARBOXYLATE synthesis

Yield:914347-01-6 41%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in acetonitrile at 20; for 16 h;

Steps:

1a.1 methyl 1-(5-bromopyrimidin-2-yl)piperidine-4-carboxylate

Step 1 : DIPEA (4 mL, 23.20 mmol) was added to 5-bromo-2-chloropyrimidine (3.0 g, 15.50 mmol) in acetonitrile (80 mL). Then, methyl isonipecotate (3.321 g, 23.20 mmol) was added to the solution. The reaction mixture was stirred at rt for Ex.9a 16h. The solvent was concentrated to dryness. Water and EtOAc were added to quench the reaction. The organic layer was separated and concentrated to dryness. The crude material was purified by silica gel column chromatography eluting with heptane and a gradient of heptane/EtOAc from [100:0] to [0:100]. The product fractions were combined and concentrated to dryness to afford methyl 1-(5-bromopyrimidin-2-yl)piperidine-4-carboxylate Ex.9a (1 .84 mg, 41 %) as white solid.

References:

WO2018/138356,2018,A1 Location in patent:Page/Page column 35; 40-41