반응 #44222

반응 방정식

2-(4-bromo-2-fluorophenylamino)-6-chloronicotinic acid

4-bromo-2-fluorophenylamine

lithium bis(trimethylsilyl)amide

2,6-Dichloro-nicotinic acid

→

pure desired product

수율 83.0%

2-(4-Bromo-2-fluorophenylamino)-6-oxo-1,6-dihydropyridine-3-carboxylic acid

수율 83.0%

용매

THF

THF

반응 조건

후처리

1. 1
   온도to warm from −78° C. to room temperature
2. 2
   workup.STIRRINGstir for 16 hours
3. 3
   기타The reaction mixture was quenched by the addition of H2O
4. 4
   workup.ADDITIONdiluted with EtOAc
5. 5
   기타The organic layer was separated
6. 6
   세척washed with H2O, saturated NaCl
7. 7
   건조dried (Na2SO4)
8. 8
   농축concentrated under reduced pressure
9. 9
   기타The crude product was triturated several times with ethyl acetate
10. 10
    기타the resulting solid was collected
11. 11
    세척washed with dichloromethane
12. 12
    기타dried under vacuum

실험 절차

Preparation of 2-(4-bromo-2-fluorophenylamino)-6-chloronicotinic acid: To a solution of 4-bromo-2-fluorophenylamine (10.4 g, 54.7 mmol) in THF (25 mL) at −78° C. under N2 was added lithium bis(trimethylsilyl)amide (83.3 mL, 83.3 mmol, 1 M solution in hexanes) dropwise over 15 minutes. The reaction mixture was stirred for one hour at −78° C. 2,6-Dichloro-nicotinic acid (5.00 g, 26.0 mmol) was then added dropwise as a solution in THF (15 mL) and the reaction mixture was allowed to warm from −78° C. to room temperature and stir for 16 hours. The reaction mixture was quenched by the addition of H2O and the pH was adjusted to 0-2 with 6 N HCl and then diluted with EtOAc. The organic layer was separated and washed with H2O, saturated NaCl, dried (Na2SO4), and concentrated under reduced pressure. The crude product was triturated several times with ethyl acetate and the resulting solid was collected, washed with dichloromethane and dried under vacuum to yield 7.50 g (83%) pure desired product as a dark pink solid.

출처