تفاعل #1269879

معادلة التفاعل

Phenol

K2CO3

DCC

4-chloronicotinic acid

ethanol

→

ethyl 4-phenoxynicotinate

المردود 51.5%

المذيبات

Water

DMF

water

ظروف التفاعل

المعالجة

1. 1
   أخرىthe solid formed
2. 2
   ترشيحwas filtered off
3. 3
   استخلاصThe filtrate was extracted with DCM
4. 4
   غسيلwashed with water
5. 5
   تجفيفdried (MgSO4)
6. 6
   أخرىthe solvent was removed in vacuo
7. 7
   workup.DISSOLUTIONThe crude ethyl 4-chloronicotinate (5.8 g) was dissolved in DMF (15 mL)
8. 8
   درجة الحرارةThe reaction mixture was heated to 80° C. for 3 h
9. 9
   درجة الحرارةto cool to room temperature
10. 10
    workup.WAITleft overnight
11. 11
    workup.STIRRINGwithout stirring
12. 12
    استخلاصextracted with EtOAc
13. 13
    غسيلThe combined organic layers were washed with aqueous NaOH solution (1 M), water
14. 14
    تجفيفdried over MgSO4
15. 15
    أخرىPurification by flash chromatography (DCM/EtOAc, gradient 1-10% EtOAc)

الإجراء التجريبي

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.

المصدر