反应详情

Methyl 2-hydroxy-3-pyrazinecarboxylate (103 mg, 0.67 mmol) (obtained from Fulcrum Scientific Ltd.) was placed in a 25-mL RBF and placed under a nitrogen atmosphere. DMF (3 mL) was added, followed by NaH (33 mg, 0.83 mmol) and the reaction was allowed to stir for twenty minutes at room temperature. 3,4-Difluorobenzyl bromide (0.094 mL, 0.735 mmol) was added, and the reaction was allowed to stir at room temperature overnight, and the reaction was found to be complete by LC-MS. The reaction was added to a separatory funnel containing ethyl acetate (125 mL) and dilute aqueous NaHCO3 (75 mL); the phases were separated and the organic layer was washed with brine and dried over anhydrous Na2SO4, then concentrated in vacuo. The crude product was purified by silica gel chromatography using 10-100% EtOAc in n-heptane to afford methyl 4-(3,4-difluorobenzyl)-3-oxo-3,4-dihydropyrazine-2-carboxylate as a yellow solid. 1H NMR (500 MHz, C2D6SO) δ 8.08 (d, 1H), 7.49 (t, 1H), 7.44 (d, 1H), 7.42 (t, 1H), 7.23 (m, 1H), 5.09 (s, 2H), 3.80 (s, 3H). LRMS (ESI) calc'd for (C13H11F2N2O3) [M+H]+, 281.1; found 281.1.

1. stirringto stir at room temperature overnight
2. additionThe reaction was added to a separatory funnel
3. customthe phases were separated
4. washthe organic layer was washed with brine
5. dry with materialdried over anhydrous Na2SO4
6. concentrationconcentrated in vacuo
7. customThe crude product was purified by silica gel chromatography