反应详情

温度

-10 °C

To a solution of 2-chloro-4-fluoro-1-iodobenzene (0.307 g, 1.199 mmol) in THF (Volume: 1.622 ml) cooled to −10° C. was added isopropylmagnesium chloride, 2M in THF (0.699 ml, 1.399 mmol) in one portion. After 30 min, 3-fluoro-4-(pyrimidin-5-yl)picolinonitrile (0.200 g, 0.999 mmol) was added. The reaction mixture was stirred at −10° C. for 30 min, then allowed to warm to room temperature and stirred 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 (24 g column, 35 mL/min, 60-100% EtOAc in hexanes over 23 min, tr=9 min) gave the title compound (0.029 g, 0.074 mmol, 7.44% yield) as an orange solid.

1. temperatureto warm to room temperature
2. stirringstirred overnight
3. stirringAfter stirring for 1 hr
4. customThe layers were separated
5. extractionThe aqueous phase was extracted with CH2Cl2 (5×)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customto afford an orange residue
10. customto be chromatographed
11. customPurification of the crude material by silica gel chromatography
12. customan ISCO machine (24 g column, 35 mL/min, 60-100% EtOAc in hexanes over 23 min, tr=9 min)