반응 #2186182

반응 방정식

hydrochloric acid

trimethyl borate

compound ( C2 )

1-bromo-3-chloro-4-ethoxy-2-fluorobenzene

magnesium

→

3-chloro-4-ethoxy-2-fluorophenylboronic acid

수율 83.3%

용매

acetic acid

THF

THF

THF

반응 조건

후처리

1. 1
   workup.ADDITIONwas added dropwise
2. 2
   기타The resulting reaction mixture
3. 3
   온도was cooled to 25° C
4. 4
   온도cooled to −50° C. over 60 minutes in a nitrogen atmosphere in a temperature range of −60 to −40° C
5. 5
   온도The reaction mixture was warmed to 0° C.
6. 6
   workup.ADDITIONby mixing
7. 7
   workup.WAITthe mixture was then left
8. 8
   기타to separate into an organic layer
9. 9
   추출by extracting
10. 10
    기타The resulting organic layer was collected
11. 11
    세척washed with a saturated sodium hydrogen carbonate aqueous solution and water
12. 12
    건조by drying over anhydrous magnesium sulfate
13. 13
    workup.DISTILLATIONThereafter, the solvent was distilled off under reduced pressure
14. 14
    기타to obtain a residue
15. 15
    기타The residue was recrystallized from heptane

실험 절차

4.79 g of well dried magnesium and 50 mL of THF were added to a reactor in a nitrogen atmosphere and heated to 50° C. 50.0 g of the compound (C2) dissolved in 200 mL of THF was added dropwise thereto over 60 minutes in a temperature range of 43 to 48° C., followed by stirring for 60 minutes. The resulting reaction mixture was cooled to 25° C. Thereafter, the reaction mixture was added dropwise to a solution of 24.6 g of trimethyl borate and 100 mL of THF cooled to −50° C. over 60 minutes in a nitrogen atmosphere in a temperature range of −60 to −40° C. The reaction mixture was warmed to 0° C. and then poured into 400 mL of 3N hydrochloric acid at 0° C. 700 mL of acetic acid was added to the solution, followed by mixing, and the mixture was then left to rest to separate into an organic layer and an aqueous layer, followed by extracting. The resulting organic layer was collected and washed with a saturated sodium hydrogen carbonate aqueous solution and water, followed by drying over anhydrous magnesium sulfate. Thereafter, the solvent was distilled off under reduced pressure to obtain a residue. The residue was recrystallized from heptane. The recrystallization operation was repeated to obtain 35.9 g of 3-chloro-4-ethoxy-2-fluorophenylboronic acid (b58). The resulting compound (b58) was a yellowish solid.

출처