反应详情

温度

0 °C

A 2.5 M solution of n-butyllithium (96 ml, 240 ml) in n-hexane was added to a solution of N,N dimethylaminoethanol (10.65 g, 120 mmol) in abs. THF (70 ml) at −5° C. under argon within 25 min. The reaction mixture was stirred for 30 min at 0° C. and cooled down to −70° C. At a temperature of −70 to −65° C., a solution of 3-chloropyridine (3.8 ml, 4.5 g, 40 mmol) in abs. THF (60 ml) was added within 10 min and stirred for a further hour at this temperature. Abs. DMF (12.3 ml, 11.7 g, 160 mmol) in THF (100 ml) was then added within 15 min at −65 to −60° C. The dark brown solution was heated within 1 h to 10° C. At a temperature of −20 to −10° C., the reaction mixture was hydrolysed with sat. ammonium chloride solution (120 ml). The mixture was then stirred for 30 min at 0° C. The phases were not separated. The organic solvents were removed under vacuum. The residue was extracted with DCM (120 ml). The phases were separated. The aqueous phase was extracted with DCM (3×120 ml). The organic phases were combined and concentrated without drying. The residue was a brown oil which was further purified by adding water (4×50 ml) and decanting. After the addition of DCM (250 ml) and sodium sulphate, the mixture was dried overnight and then concentrated. The crude product of the 3-chloropyridine-2-carbaldehyde (F) was obtained as a hydrate (brown oil 8.73 g, theoretical yield 6.3 g). Chromatographic purification of the crude product was not possible. The crude product was used without further purification.

1. temperaturecooled down to −70° C
2. customAt a temperature of −70 to −65° C.
3. stirringstirred for a further hour at this temperature
4. temperatureThe dark brown solution was heated within 1 h to 10° C
5. customAt a temperature of −20 to −10° C.
6. stirringThe mixture was then stirred for 30 min at 0° C
7. customThe phases were not separated
8. customThe organic solvents were removed under vacuum
9. extractionThe residue was extracted with DCM (120 ml)
10. customThe phases were separated
11. extractionThe aqueous phase was extracted with DCM (3×120 ml)
12. concentrationconcentrated
13. customwithout drying
14. customwas further purified
15. additionby adding water (4×50 ml)
16. customdecanting
17. additionAfter the addition of DCM (250 ml) and sodium sulphate
18. customthe mixture was dried overnight
19. concentrationconcentrated