Réaction #1269879

Équation de réaction

Phenol

K2CO3

DCC

4-chloronicotinic acid

ethanol

→

ethyl 4-phenoxynicotinate

Rendement 51.5%

Solvants

Water

DMF

water

Conditions de réaction

Traitement

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

Mode opératoire

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.

Source