反应详情

To a solution of 3-fluoro-4-(4-hydroxypyrimidin-5-yl)picolinonitrile (0.152 g, 0.703 mmol) in tetrahydrofuran (Volume: 2.344 ml) cooled to 0° C. was added (4-fluorophenyl)magnesium bromide (1.055 ml, 2.109 mmol). The reaction mixture was allowed to stir at room temperature overnight. Water and ice were carefully added, followed by acidification with 6 M HCl. After stirring for 1 hr, CH2Cl2 was added and the pH was adjusted to 8.5 with aqueous 4 M NaOH. The layers were separated. The aqueous phase was extracted with CH2Cl2 (5×). Organics combined, dried over Na2SO4, filtered, and concentrated to afford an orange residue. The crude material was dissolved in a minimal amount of CH2Cl2 to be chromatographed. Purification of the crude material by silica gel chromatography using an ISCO machine (40 g column, 40 mL/min, 0-20% MeOH in CH2Cl2 over 25 min, tr=13 min) gave the title compound (162 mg, 0.517 mmol, 73.5% yield) as a yellow residue. ESI MS (M+H)+=314.1.

1. stirringAfter stirring for 1 hr
2. customThe layers were separated
3. extractionThe aqueous phase was extracted with CH2Cl2 (5×)
4. dry with materialdried over Na2SO4
5. filtrationfiltered
6. concentrationconcentrated
7. customto afford an orange residue
8. customto be chromatographed
9. customPurification of the crude material by silica gel chromatography
10. customan ISCO machine (40 g column, 40 mL/min, 0-20% MeOH in CH2Cl2 over 25 min, tr=13 min)