Reaktion #427600

Reaktionsgleichung

6-Chloro-nicotinic acid

o-tolylmagnesium chloride

acetic acid

→

6-chloro-4-o-tolyl-nicotinic acid

Ausbeute 51.0%

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe solution obtained
2. 2
   TemperaturIt was cooled to −60° C.
3. 3
   workup.WAITAfter 30 minutes at −60° C.
4. 4
   Filtrationone hour at room temperature, the reaction mixture was filtered
5. 5
   SonstigeTHF removed under reduced pressure
6. 6
   SonstigeThe residue was partitioned between water and dichloromethane
7. 7
   Extraktionextracted
8. 8
   FiltrationThe crude product was filtered on silica gel (eluent: ethyl acetate/toluene/formic acid 20:75:5)
9. 9
   Sonstigethen partitioned between 200 ml aqueous half-saturated sodium carbonate solution and 100 ml dichloromethane
10. 10
    WaschenThe organic phase was washed with 50 ml aqueous half-saturated sodium carbonate solution
11. 11
    Extraktionextracted with dichloromethane
12. 12
    TrocknenThe organic extracts were dried (Na2SO4)
13. 13
    Einengenconcentrated under reduced pressure

Vorschrift

13.0 g (82.5 mMol) 6-Chloro-nicotinic acid in 65 ml THF were cooled to 0° C. and 206.3 ml (206.3 mMol) o-tolylmagnesium chloride solution (1M in THF) were added over 45 minutes. The solution obtained was further stirred 3 hours at 0° C. and overnight at room temperature. It was cooled to −60° C. and 103.8 ml (1.8 Mol) acetic acid were added, followed by 35 ml THF and 44.24 g (165 mMol) manganese(III) acetate dihydrate. After 30 minutes at −60° C. and one hour at room temperature, the reaction mixture was filtered and THF removed under reduced pressure. The residue was partitioned between water and dichloromethane and extracted. The crude product was filtered on silica gel (eluent: ethyl acetate/toluene/formic acid 20:75:5) then partitioned between 200 ml aqueous half-saturated sodium carbonate solution and 100 ml dichloromethane. The organic phase was washed with 50 ml aqueous half-saturated sodium carbonate solution, The combined aqueous phases were acidified with 25 ml aqueous HCl 25% and extracted with dichloromethane. The organic extracts were dried (Na2SO4) and concentrated under reduced pressure to yield 10.4 g (51%) of 6-chloro-4-o-tolyl-nicotinic acid as a yellow foam. MS (ISN): 246 (M−H, 100), 202 (M-CO2H, 85), 166 (36).

Quelle