반응 #426865

반응 방정식

2-Bromo-4-fluorobenzenamine

NH4OH

water

2-bromo-4-fluorobenzenamine

(E)-but-2-enal

→

desired product

수율 85.0%

8-bromo-6-fluoro-2-methylquinolin

수율 85.0%

용매

HCl

반응 조건

후처리

1. 1
   온도The reaction mixture was then heated
2. 2
   온도to reflux
3. 3
   workup.ADDITIONmixed with 1.0 mL
4. 4
   기타over 25 minutes
5. 5
   workup.ADDITIONaddition the reaction
6. 6
   기타had been consumed
7. 7
   workup.ADDITIONfollowed by addition of 50 mL of Et2O
8. 8
   기타followed by removal of Et2O
9. 9
   기타by partitioning
10. 10
    workup.ADDITIONwas then added in two portions
11. 11
    온도by cooling to 0° C. over 30 minutes
12. 12
    기타The pH of the crude reaction mixture
13. 13
    추출The crude mixture was then extracted with Et2O
14. 14
    건조The combined organics were then dried over Na2SO4
15. 15
    농축concentrated in vacuo

실험 절차

2-Bromo-4-fluorobenzenamine (10 g, 52.6 mmol) was weighed into a round bottom flask, and dissolved in 40 mL of 6N HCl. The reaction mixture was then heated to reflux, followed by drop-wise addition of (E)-but-2-enal (4.578 mL, 55.3 mmol) mixed with 1.0 mL deionized water over 25 minutes. Following complete addition the reaction was heated at 100° C. for an additional 35 minutes, until all the 2-bromo-4-fluorobenzenamine had been consumed. The reaction was cooled to ambient temperature, followed by addition of 50 mL of Et2O. The reaction was stirred for 5 minutes followed by removal of Et2O by partitioning. The aqueous layer was replaced into the original reaction flask and ZnCl2 (3.586 g, 26.3 mmol) was then added in two portions followed by cooling to 0° C. over 30 minutes. The pH of the crude reaction mixture was then adjusted to pH=8.0 using concentrated NH4OH. The crude mixture was then extracted with Et2O, followed by ethyl acetate. The combined organics were then dried over Na2SO4, and then concentrated in vacuo, affording the desired product as a brown solid (10.7 g, 85% yield). MS APCI (+) m/z 240.2 and 242.2 (M+1 of each Br isotope) detected.

출처