反応 #2186182

反応方程式

hydrochloric acid

trimethyl borate

compound ( C2 )

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

magnesium

→

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

収率 83.3%

溶媒

acetic acid

THF

THF

THF

反応条件

後処理

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

実験手順

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.

出典