2,2,6,6-Tetramethylpiperidine → HCID 86677186, compound

Participants

Reaction Conditions

Reaction Steps

2,2,6,6-tetramethylpiperidine (1.729 g, 2.066 mL, 12.24 mmol) was dissolved in THF (20.00 mL) and cooled to −30° C. under nitrogen. BuLi (4.488 mL of 2.5 M, 11.22 mmol) was added dropwise and the reaction allowed to warm to 0° C. Stir at this temperature for 10 minutes then cooled to −78° C. A solution of 2-fluoropyrazine (1 g, 10.20 mmol) in THF (4.000 mL) was added slowly and the mixture stirred at −78° C. for 1 h. Methyl 6-chloropyridine-2-carboxylate (1.750 g, 10.20 mmol) in THF (6.000 mL) was added dropwise at between −78 and −70° C., stirred at −78° C. for 1 h. Reaction quenched with 5% citric acid at −78° C. then allow to warm to ambient temperature. Diluted with EtOAc and separated layers. Extracted with EtOAc (x1) then wash combined organics with NaHCO3 (x1), brine (x1). Dried (MgSO4), filtered and concentrated. Crude product purified by ISCO companion (80 g SiO2, 0 to 50% EtOAc/petrol) to leave title compound as an orange oil (1.12 g, 46%). 1H NMR (DMSO-d6) δ 7.90 (dd, 1H), 8.22-8.15 (dd, 2H), 8.67 (dd, 1H), 8.84 (dd, 1H). ES+238.13.

Provenance & Evidence