[Mg].Br[C:3]1[CH:8]=[CH:7][C:6]([O:9][CH2:10][CH3:11])=[C:5]([Cl:12])[C:4]=1[F:13].[B:14](OC)([O:17]C)[O:15]C.C(OCC)(=O)C>C1COCC1.Cl>[Cl:12][C:5]1[C:4]([F:13])=[C:3]([B:14]([OH:17])[OH:15])[CH:8]=[CH:7][C:6]=1[O:9][CH2:10][CH3:11]4.79 g of well dried magnesium and 50 mL of THF were placed in a reactor under nitrogen atmosphere, and heated to 50° C. 50.0 g of the compound (1) dissolved in 200 mL of THF was added dropwise thereto at a temperature range of from 43 to 48° C. over 60 minutes, followed by stirring for 60 minutes. The reaction mixture was cooled to 25° C. Thereafter, the resulting reaction mixture was added dropwise to a solution of 24.6 g of trimethyl borate and 100 mL of THF having been cooled to −50° C. in a nitrogen atmosphere at a temperature range of from −60 to −40° C. over 60 minutes. The reaction mixture was warmed to 0° C. and then put in 400 mL of 3N hydrochloric acid at 0° C. 700 mL of ethyl acetate was added to and mixed with the resulting solution, and separated into an organic layer and an aqueous layer by standing still, so as to attain extraction to the organic layer. The resulting organic layer was fractionated and washed with a saturated sodium bicarbonate aqueous solution and water, followed by drying over anhydrous magnesium sulfate. Thereafter, the solvent was removed by distillation under reduced pressure to obtain a residue. The residue was recrystallized from heptane. The recrystallization operation was again repeated to obtain 35.9 g of 3-chloro-4-ethoxy-2-fluorophenylboronic acid (12). The resulting compound (12) was a pale yellow solid matter.
読み込み中…
