Trimethyl borate → 3-Cyano-4-fluorophenylboronic acid

HRID 1821040Notes

Reaction equation

HRID 1821040 reaction equation
C[O:2][B:3]([O:6]C)OC.Br[C:9]1[CH:10]=[CH:11][C:12]([F:17])=[C:13]([CH:16]=1)[C:14]#[N:15].C([Li])CCC>C1(C)C=CC=CC=1.C1COCC1>[C:14]([C:13]1[CH:16]=[C:9]([B:3]([OH:6])[OH:2])[CH:10]=[CH:11][C:12]=1[F:17])#[N:15]

Participants

6

Reactant 3

HCID 8470Trimethyl borateHCID 27249005-Bromo-2-fluorobenzonitrileHCID 178418339Butyllithium

Product 1

HCID 27579643-Cyano-4-fluorophenylboronic acidYield 20%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Procedure

Trimethylborate (1.37 mL, 12 mmol) was added to a solution of 5-bromo-2-fluorobenzonitrile (2.0 g, 10 mmol) in toluene (16 mL) and THF (4 mL) at −78° C. n-Butyl lithium (2.5M in hexane; 4.8 mL) was slowly added over 1 h and the solution was stirred for 30 min after which it was warmed to rt for 1 h. The reaction was cooled to 0° C. and quenched with 20 mL of 1 N HCl. The product was extracted with ethyl acetate (2×200 mL), dried over magnesium sulfate, filtered and concentrated in vacuo. Silica gel chromatography eluting with 5% methanol/methylene chloride afforded 0.33 g of the desired product.

Workup

  1. additionwas slowly added over 1 h
  2. temperatureThe reaction was cooled to 0° C.
  3. customquenched with 20 mL of 1 N HCl
  4. extractionThe product was extracted with ethyl acetate (2×200 mL)
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. washSilica gel chromatography eluting with 5% methanol/methylene chloride

Sources & evidence

ORD record
ord-885dc9fcc8f1465fa8158a77e60829bf
Source dataset
uspto-grants-2009_10
Patent number
US07605171B2

Reaction notes

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