反应 #1269879

反应方程式

Phenol

K2CO3

DCC

4-chloronicotinic acid

ethanol

→

ethyl 4-phenoxynicotinate

收率 51.5%

溶剂

Water

DMF

water

反应条件

后处理

1. 1
   其他the solid formed
2. 2
   过滤was filtered off
3. 3
   萃取The filtrate was extracted with DCM
4. 4
   洗涤washed with water
5. 5
   干燥dried (MgSO4)
6. 6
   其他the solvent was removed in vacuo
7. 7
   workup.DISSOLUTIONThe crude ethyl 4-chloronicotinate (5.8 g) was dissolved in DMF (15 mL)
8. 8
   温度The reaction mixture was heated to 80° C. for 3 h
9. 9
   温度to cool to room temperature
10. 10
    workup.WAITleft overnight
11. 11
    workup.STIRRINGwithout stirring
12. 12
    萃取extracted with EtOAc
13. 13
    洗涤The combined organic layers were washed with aqueous NaOH solution (1 M), water
14. 14
    干燥dried over MgSO4
15. 15
    其他Purification by flash chromatography (DCM/EtOAc, gradient 1-10% EtOAc)

实验过程

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.

来源