Reaktion #44192

Reaktionsgleichung

nBuLi

diisopropylamine

4,6-dichloro-5-fluoro-nicotinic acid

4-bromo-2-fluorophenylamine

→

clean desired product

Ausbeute 72.1%

4-(4-bromo-2-fluorophenylamino)-6-chloro-5-fluoro-nicotinic acid

Ausbeute 72.1%

Lösungsmittel

THF

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITAfter 20 minutes
2. 2
   workup.WAITAfter 10 minutes
3. 3
   Temperaturto warm to room temperature
4. 4
   SonstigeAfter quenching the reaction mixture with 10% HCl (20 mL), it
5. 5
   Extraktionwas extracted with ethyl acetate
6. 6
   TrocknenThe combined organic extracts were dried (MgSO4)
7. 7
   Einengenconcentrated under reduced pressure

Vorschrift

nBuLi (14.7 mL, 36.7 mmol, 2.5 M solution in hexanes) was added to a stirred solution of diisopropylamine (5.15 mL, 36.7 mmol) in THF (20 mL) at 0° C. After 20 minutes, the reaction mixture was cooled to −78° C. and a solution of 4-bromo-2-fluorophenylamine (4.65 g, 24.5 mmol) in THF (10 mL) was added. After 20 minutes, a solution of 4,6-dichloro-5-fluoro-nicotinic acid (Sanchez et al J Heterocylc. Chem. 1993, 30 (4), 855-9) (2.57 g, 12.25 mmol) in THF (10 mL) was added. After 10 minutes, the reaction mixture was allowed to warm to room temperature and stirred for 1 hour. After quenching the reaction mixture with 10% HCl (20 mL), it was extracted with ethyl acetate. The combined organic extracts were dried (MgSO4) and concentrated under reduced pressure. Trituration with methylene chloride yielded 3.21 g (72%) of clean desired product.

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