Methyl iodide → Tert-butyl 4-[(6-chloropyrazin-2-yl)(methyl)amino]piperidine-1-carboxylate

Temperature

0 °C

To a stirred solution of tert-butyl 4-[(6-chloropyrazin-2-yl)amino]piperidine-1-carboxylate (0.165 g, 0.528 mmol) in THF (2.6 ml) was added methyl iodide (0.165 ml, 2.64 mmol). The solution was cooled to 0° C., and a solution of NaHMDS in THF (1M; 1.06 ml, 1.06 mmol) was added. The reaction mixture was allowed to warm to room temperature and stirred for 2 h. The reaction was quenched with saturated aqueous ammonium chloride (50 mL, and extracted with EtOAc (2×50 mL). The combined EtOAc layers were washed with brine (50 mL), dried over magnesium sulfate, filtered and concentrated. The crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient) to afford tert-butyl 4-[(6-chloropyrazin-2-yl)(methyl)amino]piperidine-1-carboxylate as a yellow oil. LRMS calculated for C15H23ClN4O2 [M+Na]+, 349.2; found 349.0.

1. temperatureto warm to room temperature
2. customThe reaction was quenched with saturated aqueous ammonium chloride (50 mL
3. extractionextracted with EtOAc (2×50 mL)
4. washThe combined EtOAc layers were washed with brine (50 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude residue was purified by silica gel chromatography (EtOAc/Hexanes gradient)

ORD record

ord-64963f822972416c8cdd03d5bef98f5a

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08183245B2