反应详情

POBr3 (6.65 g, 23.2 mmol, Spectrochem) was added to a stirred solution of methyl 6-hydroxy-2-methylpyrimidine-4-carboxylate (5.0 g, 29.7 mmol, Preparation #2) in DMF (100 mL) at about 90° C. The reaction mixture was heated at the same temperature for about another 10 min and poured into ice water (500 mL). The solution was neutralized with 10% aqueous sodium carbonate solution (pH 7). This solution was extracted with EtOAc (3×200 mL). The combined organic layer was washed with water (2×100 mL) and brine solution (2×150 mL), and dried over sodium sulphate and concentrated in vacuum. The crude material was purified by silica gel chromatography using 15 to 25% of EtOAc in hexane as the eluent. Relevant fractions containing the required compound were combined and evaporated to dryness under reduced pressure to afford methyl 6-bromo-2-methylpyrimidine-4-carboxylate as an off white solid 5.2 g (75.7%). 1H NMR (400 MHz, DMSO) δ: 8.02 (s, 1H), 4.03 (s, 3H), 2.83 (s, 3H); MS m/z: 231 (M+H)+.

1. temperatureThe reaction mixture was heated at the same temperature for about another 10 min
2. extractionThis solution was extracted with EtOAc (3×200 mL)
3. washThe combined organic layer was washed with water (2×100 mL) and brine solution (2×150 mL)
4. dry with materialdried over sodium sulphate
5. concentrationconcentrated in vacuum
6. customThe crude material was purified by silica gel chromatography
7. additionRelevant fractions containing the required compound
8. customevaporated to dryness under reduced pressure