Reaktion #1525491

Reaktionsgleichung

5,6 dichloronicotinic acid

isobutyronitrile

BH3.THF

K2CO3

potassium hexamethyldisilazide

→

title compound

Ausbeute 32.1%

2-(3-Chloro-5-hydroxymethyl-pyridin-2-yl)-2-methyl-propionitrile

Ausbeute 32.1%

Lösungsmittel

THF

THF

water

toluene

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeSolvents were removed
2. 2
   SonstigeThe layers of the resulting reaction mixture
3. 3
   Sonstigewere separated
4. 4
   Extraktionthe aqueous layer was extracted three additional times with ethyl acetate
5. 5
   Trocknendried over Na2SO4
6. 6
   Filtrationfiltered
7. 7
   Einengenconcentrated in vacuo to a yellow solid (3.34 g)
8. 8
   workup.DISSOLUTIONThis crude residue was dissolved in THF (80 mL)
9. 9
   Sonstigereaction
10. 10
    Temperaturcooled to 0° C
11. 11
    Sonstigereaction
12. 12
    workup.STIRRINGstirred at 0° C. for 4 hours
13. 13
    Sonstigeroom temperature overnight
14. 14
    Extraktionthe aqueous layer was extracted three additional times with ethyl acetate
15. 15
    TrocknenThe organics were combined dried over Na2SO4
16. 16
    Filtrationfiltered
17. 17
    Einengenconcentrated in vacuo to a clear oil which
18. 18
    Sonstigewas purified by silica gel chromatography (hexanes)

Vorschrift

To a magnetically stirring solution of 5,6 dichloronicotinic acid (2.7 g, 14.06 mmol) in THF (70.0 mL), was added isobutyronitrile (6.37 mL, 69.66 mmol) followed by potassium hexamethyldisilazide 0.5 M in toluene (70 mL). The resulting orange mixture was stirred at 60° C. overnight. Solvents were removed and residue portioned between ethyl acetate (100 mL) and 1N HCl (100 mL). The layers of the resulting reaction mixture were separated and the aqueous layer was extracted three additional times with ethyl acetate. The organic layers were combined and dried over Na2SO4, filtered and concentrated in vacuo to a yellow solid (3.34 g). This crude residue was dissolved in THF (80 mL) and reaction cooled to 0° C. BH3.THF 1 M solution in THF (22.30 mL) was added and reaction stirred at 0° C. for 4 hours, then room temperature overnight. Solid K2CO3 (2 g) and water (100 mL) were added and the aqueous layer was extracted three additional times with ethyl acetate. The organics were combined dried over Na2SO4, filtered and concentrated in vacuo to a clear oil which was purified by silica gel chromatography (hexanes) to give the title compound as a white solid (0.95 g, 32%). ESIMS (MH+): 210.

Quelle