Pyrazine, 2-chloro-6-(tributylstannyl)- synthesis

Yield:850221-68-0 71.5%

Reaction Conditions:

with 2,2,6,6-tetramethyl-piperidine;n-butyllithium in tetrahydrofuran;hexane at -78 - -40;

Steps:

4

Preparation of compound 4a: 2-chloro-6-(tributylstannyl)pyrazineTo a solution of nBuLi, 1.6m in hexane (21.49 mL, 34.4 mmol) in THF (80 mL) at -50 °C was added 2,2,6,6-tetramethylpiperidine (5.80 mL, 34.4 mmol). The mixture was warmed to 0 °C and stirred for 20 min. The mixture was then cooled to -78 °C. In another flask, 2-chloropyrazine (0.974 mL, 10.91 mmol) and tributyltin chloride (2.96 mL, 10.91 mmol) were dissolved in THF (50 mL) and cooled to -78 °C. The cooled solution was transferred to lithium solution through cannula and the resulting orange mixture was slowly warmed up to -40 °C in 3 h, and was quenched with sat.HCl:EtOH:THF (1 :4:5, 50 mL) and warmed to RT. The mixture was neutralized with sat. NaHCO^ and the volatiles were removed. The residue was diluted in H₂0 and extracted with DCM. The combined organic layers were dried, filtered and concentrated. The residue was purified with silica gel chromatography (eluting with 0-30% DCM in Hex) to give 2-chloro-6-(tributylstannyl)pyrazine (3.15 g, 7.81 mmol, 71.5 % ) as a clear oil. MS (ESI, pos. ion) m/z: 405 (M+l). ^.H NMR (400 MHz, CDCl₃) δ ppm 8.42 (1 H, s), 8.38 (1 H, s), 1.50 - 1.62 (6 H, m), 1.27 - 1.41 (6 H, m), 1.14 - 1.22 (6 H, m), 0.89 (9 H, t, J=7.3 Hz)

References:

WO2012/129338,2012,A1 Location in patent:Page/Page column 74-75