Reaction #2186182

Reaction equation

hydrochloric acid

trimethyl borate

compound ( C2 )

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

magnesium

→

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

Yield 83.3%

Solvents

acetic acid

THF

THF

THF

Conditions

Workup

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

Procedure

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.

Source