Acetic Acid → (5-Bromo-2-fluorophenyl)boronic acid

HRID 1531474Notes

Reaction equation

C([N-]C(C)C)(C)C.[Li+].[Br:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[CH:12][CH:11]=1.[B:17](OC)([O:20]C)[O:18]C.C(O)(=O)C>O1CCCC1.C(OCC)C.O>[Br:9][C:10]1[CH:15]=[CH:14][C:13]([F:16])=[C:12]([B:17]([OH:20])[OH:18])[CH:11]=1

Participants

Conditions

Temperature: -70 °C

Procedure

A solution of lithium diisopropylamide (165 mL of a 2.0 M solution in tetrahydrofuran, 0.33 mol) in tetrahydrofuran (600 mL) at −70° C. is treated with 1-bromo-4-fluorobenzene (33.0 mL, 0.30 mol), stirred at −70° C. for 90 minutes and added to a solution of trimethyl borate (41.0 mL, 0.36 mol) in diethyl ether (300 mL) at −70° C. The resulting solution is stirred at −70° C. for 15 minutes, warmed to 15° C. over 90 minutes, treated with acetic acid (51.5 mL, 0.9 mol) and water (375 mL), and stirred at room temperature for 30 minutes. The organic layer is separated and the aqueous layer is extracted with ether. The organic extracts are combined with the organic layer and the resulting solution is washed sequentially with 10% hydrochloric acid and brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to give the title product as an off-white solid (65 g, 99% yield).

Workup

stirringThe resulting solution is stirred at −70° C. for 15 minutes
temperaturewarmed to 15° C. over 90 minutes
stirringstirred at room temperature for 30 minutes
customThe organic layer is separated
extractionthe aqueous layer is extracted with ether
washthe resulting solution is washed sequentially with 10% hydrochloric acid and brine
dry with materialdried over anhydrous magnesium sulfate
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-129df2ea92bf42cfb05dfc459d1519e6
Source dataset: uspto-grants-2001_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06198008B1

Reaction notes

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