تفاعل #745666

معادلة التفاعل

5-hydroxynicotinic acid methyl ester

sodium hydride

2,3-difluoro-4-nitrobenzene

→

5-(4-nitro-3-fluorophenoxy)nicotinic acid methyl ester

المردود 28.0%

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGthe reaction mixture was stirred at room temperature
2. 2
   أخرىAfter 3 hours the solvent was removed under reduced pressure
3. 3
   أخرىthe residue was partitioned between EtOAC (300 mL) and H2O (150 mL)
4. 4
   استخلاصThe aqueous layer was extracted with EtOAc (100 mL)
5. 5
   تجفيفthe combined organic layers were dried over Na2SO4
6. 6
   ترشيحfiltered
7. 7
   أخرىthe filtrate removed under reduced pressure
8. 8
   أخرىThe crude product was purified by column chromatography
9. 9
   غسيلeluted with 50 to 75% EtOAc/Hex

الإجراء التجريبي

To an ice bath cooled solution of 5-hydroxynicotinic acid methyl ester (5.00 g, 32.65 mmol) in DMF (20 mL) was added sodium hydride (0.78 g, 32.65 mmol). The reaction mixture was stirred at room temperature for 2 hours, and 2,3-difluoro-4-nitrobenzene (5.12 g, 29.68 mmol) was added, and the reaction mixture was stirred at room temperature. After 3 hours the solvent was removed under reduced pressure, and the residue was partitioned between EtOAC (300 mL) and H2O (150 mL). The aqueous layer was extracted with EtOAc (100 mL), and the combined organic layers were dried over Na2SO4, filtered, and the filtrate removed under reduced pressure. The crude product was purified by column chromatography eluted with 50 to 75% EtOAc/Hex to give 2.4 g (28%) of 5-(4-nitro-3-fluorophenoxy)nicotinic acid methyl ester. 1H-NMR (CD3OD) δ 9.05 (d, J=1.8 Hz, 1H), 8.70 (d, J=2.7 Hz, 1H), 8.31 (dd, J=2.4, 10.5 Hz, 1H), 8.15-8.14 (m, 1H), 9.06 (dd, J=1.5, 2.1 Hz, 1H), 7.40 (dd, J=8.1, 9.0 Hz, 1H), 3.97 (s, 3H); MS LC-MS [M+H]+=293.1; RT=3.15 min.

المصدر