Reacción #168654

Ecuación de reacción

2-chloropyrazine

NaHCO3

2,2,6,6 Tetramethyl piperidine

n-Butyl lithium

Pyridine-3-carbaldehyde

→

(3-chloro-pyrazin-2-yl)-pyridin-3-yl-methanol

Disolventes

THF

Condiciones de reacción

Tratamiento posterior

1. 1
   workup.STIRRINGthe reaction stirred at this temperature for 35 minutes
2. 2
   TemperaturaThe reaction is cooled to −78° C.
3. 3
   Otroto form a red solution, which
4. 4
   workup.STIRRINGis stirred at −78° C. for 40 minutes
5. 5
   workup.STIRRINGstirred at −78° C. for 1 hour and 40 minutes
6. 6
   OtroThe reaction is quenched
7. 7
   Otroat −78° C.
8. 8
   Otrothe reaction
9. 9
   Temperaturato warm slowly to room temperature
10. 10
    Extracciónthe product extracted into ethyl acetate (2×200 ml)
11. 11
    Secadodried (MgSO4)
12. 12
    Otrothe solvent removed in vacuo
13. 13
    Otroto afford a black oil which
14. 14
    Otrois purified

Procedimiento

2,2,6,6 Tetramethyl piperidine (1.97 ml, 11.6 mmol) is added dropwise to a solution o of n-Butyl lithium (6.87 ml, 11.0 mmol of 1.6 M solution in THF) in THF (40 ml) at −78° C., and the resulting solution stirred at this temperature for 5 minutes. The reaction mixture is allowed to warm to 0° C. and the reaction stirred at this temperature for 35 minutes. The reaction is cooled to −78° C., and 2-chloropyrazine (0.78 ml, 8.73 mmol) is added dropwise to form a red solution, which is stirred at −78° C. for 40 minutes. Pyridine-3-carbaldehyde (0.93 ml, 9.95 mmol) is added dropwise and stirred at −78° C. for 1 hour and 40 minutes. The reaction is quenched using 5M HCl (5 ml) at −78° C. and the reaction then allowed to warm slowly to room temperature. The pH is adjusted to 7 by the addition of sat. aq. NaHCO3 solution, and the product extracted into ethyl acetate (2×200 ml), dried (MgSO4) and the solvent removed in vacuo to afford a black oil which is purified using flash chromatography (SiO2, iso-hexane/EtOAc) to afford (3-chloro-pyrazin-2-yl)-pyridin-3-yl-methanol as a pale brown solid [M+H]+ 222.

Fuente