反应详情

温度

65 °C

6.93 g (29.9 mmol) of 4-bromobenzaldehyde dimethyl acetal in 40 ml of THF are added dropwise to a warm (from 40° C. to 50° C.) suspension of 0.8 g (31.6 mmol) of magnesium turnings and a small amount of iodine in 10 ml of THF. The reaction mixture is heated to 65° C. and stirred at that temperature for about 30 min. The mixture is allowed to cool to room temperature and the Grignard reagent is added dropwise to a solution of 4.46 g (28.2 mmol) of 2-bromopyridine (Fluka, Buchs, Switzerland) and 0.4 g (0.74 mmol) of DPPP (Fluka, Buchs, Switzerland) in 100 ml of THF (slightly exothermic reaction). After the dropwise addition is complete, the reaction mixture is boiled under reflux for 4 hours and is then allowed to cool; 100 ml of water are added. The mixture is concentrated to about 50 ml using a rotary evaporator, diluted with ethyl acetate and extracted with 0.1N hydrochloric acid (3×). The combined HCl extracts are stirred at room temperature for 20 min, rendered basic with concentrated ammonia solution and extracted with methylene chloride. After removal of the solvent, the residue is chromatographed on silica gel (hexane/ethyl acetate 2:1). The product-containing fractions are concentrated, with the desired title compound crystallising out spontaneously. TLC: Rf=0.22 (hexane/ethyl acetate 2:1). HPLC20-100: tRet=6.08. 1H-NMR (CDCl3; 200 MHz): 8.73/d, J=5 (2H); 8.16 and 7.97/each d (2×2H); 7.80/d, J=4 (2H); 7.3/m (1H).

1. temperaturea warm
2. temperatureto cool to room temperature
3. customslightly exothermic reaction)
4. additionAfter the dropwise addition
5. temperatureunder reflux for 4 hours
6. temperatureto cool
7. concentrationThe mixture is concentrated to about 50 ml
8. customa rotary evaporator
9. additiondiluted with ethyl acetate
10. extractionextracted with 0.1N hydrochloric acid (3×)
11. stirringThe combined HCl extracts are stirred at room temperature for 20 min
12. extractionextracted with methylene chloride
13. customAfter removal of the solvent
14. customthe residue is chromatographed on silica gel (hexane/ethyl acetate 2:1)
15. concentrationThe product-containing fractions are concentrated, with the desired title compound
16. customcrystallising out spontaneously