反应详情

Piperidine (0.48 ml, 4.82 mmol, 2.0 eq) was added portion-wise to a acetonitrile (2 ml) solution of 5-bromo-6-(4-fluoro-phenyl)-pyrazine-2-carboxylic acid methyl ester (0.75 g, 2.41 mmol, 1.0 eq) at room temperature. The mixture was irradiated at 100° C. in a microwave with stirring for 30 minutes. HPLC-MS indicated complete consumption of starting material. The crude mixture was cooled to room temperature concentrated. The residue was re-dissolved in ethyl acetate (10 ml), washed with water (5 ml) and the organic phase dried over MgSO4. Following filtration and evaporation in vacuo, the residue was purified by chromatography on silica gel using a gradient of heptane to 10% ethyl acetate in heptane to afford 6-(4-fluoro-phenyl)-5-piperidin-1-yl-pyrazine-2-carboxylic acid methyl ester. Yield=0.48 g (63%). 1H NMR (250 MHz, CDCl3): δ 1.42-1.53 (6H, m), 3.20-3.24 (4H, m), 3.88 (3H, s), 7.06 (2H, t, J=8.78 Hz), 7.74-7.80 (2H, m), 8.68 (1H, s).

1. customThe mixture was irradiated at 100° C. in a microwave
2. customconsumption of starting material
3. concentrationconcentrated
4. dissolutionThe residue was re-dissolved in ethyl acetate (10 ml)
5. washwashed with water (5 ml)
6. dry with materialthe organic phase dried over MgSO4
7. filtrationfiltration and evaporation in vacuo
8. customthe residue was purified by chromatography on silica gel using a gradient of heptane to 10% ethyl acetate in heptane