反应详情

温度

-10 °C

To a stirred suspension of magnesium turnings (2.6 g, 109 mmol) in anhydrous tetrahydrofuran under argon (10 mL), a solution of 1-bromo-3,5-difluoro-benzene (21 g, 109 mmol) in dry tetrahydrofuran (90 mL) was slowly added. The reaction mixture was stirred and heated at 90° C. until all magnesium was consumed (1 hour). Thereafter, the reaction was cooled at −10° C. and a solution of 2-fluoro-5-formyl-benzonitrile (13.5 g, 90.6 mmol) in 100 mL of anhydrous tetrahydrofuran was added during 30 min. After 1 hour, the reaction mixture was quenched by adding dropwise 200 mL of 20% ammonium chloride solution. Ethyl acetate was added, the layers were separated, and the aqueous layer was extracted twice with ethyl acetate. Organic layers were collected, washed with brine, dried and evaporated. Crude was triturated with isopropyl ether/hexane 1:1 (100 mL), filtered and washed with the same mixture (50 mL) to afford 16 gr of final product. Purification of the resulting organic phase by chromatography over silica gel (hexane/EtOAc 4:1) afforded 4.5 g of the title compound (total amount 20.5 g, 87% yield).

1. customwas consumed (1 hour)
2. customthe reaction mixture was quenched
3. additionby adding dropwise 200 mL of 20% ammonium chloride solution
4. additionEthyl acetate was added
5. customthe layers were separated
6. extractionthe aqueous layer was extracted twice with ethyl acetate
7. customOrganic layers were collected
8. washwashed with brine
9. customdried
10. customevaporated
11. customCrude was triturated with isopropyl ether/hexane 1:1 (100 mL)
12. filtrationfiltered
13. washwashed with the same mixture (50 mL)