Reaktion #1269879

Reaktionsgleichung

Phenol

K2CO3

DCC

4-chloronicotinic acid

ethanol

→

ethyl 4-phenoxynicotinate

Ausbeute 51.5%

Lösungsmittel

Water

DMF

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe solid formed
2. 2
   Filtrationwas filtered off
3. 3
   ExtraktionThe filtrate was extracted with DCM
4. 4
   Waschenwashed with water
5. 5
   Trocknendried (MgSO4)
6. 6
   Sonstigethe solvent was removed in vacuo
7. 7
   workup.DISSOLUTIONThe crude ethyl 4-chloronicotinate (5.8 g) was dissolved in DMF (15 mL)
8. 8
   TemperaturThe reaction mixture was heated to 80° C. for 3 h
9. 9
   Temperaturto cool to room temperature
10. 10
    workup.WAITleft overnight
11. 11
    workup.STIRRINGwithout stirring
12. 12
    Extraktionextracted with EtOAc
13. 13
    WaschenThe combined organic layers were washed with aqueous NaOH solution (1 M), water
14. 14
    Trocknendried over MgSO4
15. 15
    SonstigePurification by flash chromatography (DCM/EtOAc, gradient 1-10% EtOAc)

Vorschrift

DCC (5.24 g, 25.4 mmol) was added in portions over 10 min to a solution of 4-chloronicotinic acid (2.00 g, 12.7 mmol), ethanol (1.75 g, 38.1 mmol) and DMAP (0.19 g, 1.52 mmol) in DMF (20 mL) at 0° C. After stiffing for 1 h the reaction mixture was allowed to warm to room temperature and stirred overnight. Water (100 mL) was added and the solid formed was filtered off. The filtrate was extracted with DCM, washed with water, dried (MgSO4) and the solvent was removed in vacuo. The crude ethyl 4-chloronicotinate (5.8 g) was dissolved in DMF (15 mL). Phenol (2.86 g, 30.4 mmol), copper powder (0.48 g, 7.59 mmol), copper iodide (0.72 g, 3.80 mmol) and K2CO3 (4.20 g, 30.4 mmol) were added. The reaction mixture was heated to 80° C. for 3 h then allowed to cool to room temperature and left overnight without stirring. The mixture was poured into water and extracted with EtOAc. The combined organic layers were washed with aqueous NaOH solution (1 M), water and dried over MgSO4. Purification by flash chromatography (DCM/EtOAc, gradient 1-10% EtOAc) provided ethyl 4-phenoxynicotinate (1.59 g, 51% over 2 steps). ESI-MS [M+H]+=244.1.

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