Triisopropyl borate → (4-Methoxy-2-methylphenyl)boronic acid

HRID 2216950Notes

Reaction equation

HRID 2216950 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[CH3:10].C([Li])CCC.[B:16](OC(C)C)([O:21]C(C)C)[O:17]C(C)C>C1COCC1.CCCCCC>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([B:16]([OH:21])[OH:17])=[C:3]([CH3:10])[CH:4]=1

Participants

6

Reactant 3

HCID 21531Triisopropyl borateHCID 1179151-Bromo-4-methoxy-2-methylbenzeneHCID 178418339Butyllithium

Product 1

HCID 2773486(4-Methoxy-2-methylphenyl)boronic acidYield 76.3%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

A solution of 4-bromo-3-methylanisole (7, 92 g, 0.457 mol) in anhydrous THF (400 ml) was treated dropwise with a solution of n-butyl lithium (2.5 M solution in hexane, 201 mL, 0.503 mol, 1.1 equiv) in hexane at −60–−65° C. under N2. The resulting reaction mixture was stired at −60–65° C. for an additional 30 min before being treated dropwise with B(OiPr)3 (94.56 g, 116 mL, 0.503 mol, 1.1 equiv) at −60–−65° C. The reaction mixture was stirred at −60–−65° C. for an additional 1 h. The reaction was then quenched with saturated NH4Cl aqueous solution (400 mL) at −60–−65° C., and the resulting mixture was gradually warmed to 0° C. for 1 h and subsequently to room temperature. The two layers were separated, and the aqueous layer was extracted with EtOAc/THF (1:1, 200 mL). The combined organic extracts were then washed with H2O (200 mL), and saturated NaCl aqueous solution (200 mL), dried over MgSO4, and concentrated in vacuo. The residual white solids were then suspended in heptane (400 mL), and the resulting suspension was stirred at room temperature for 30 min. The solids were collected by filtration and washed with heptane (2×100 mL), dried in vacuo at 40–45° C. for overnight. The crude product (8, 57.9 g, 75.86 g theoretical, 76.3%) was obtained as a white powder.

Workup

  1. customThe resulting reaction mixture
  2. customThe reaction was then quenched with saturated NH4Cl aqueous solution (400 mL) at −60–−65° C.
  3. customThe two layers were separated
  4. extractionthe aqueous layer was extracted with EtOAc/THF (1:1, 200 mL)
  5. washThe combined organic extracts were then washed with H2O (200 mL), and saturated NaCl aqueous solution (200 mL)
  6. dry with materialdried over MgSO4
  7. concentrationconcentrated in vacuo
  8. stirringthe resulting suspension was stirred at room temperature for 30 min
  9. filtrationThe solids were collected by filtration
  10. washwashed with heptane (2×100 mL)
  11. customdried in vacuo at 40–45° C. for overnight

Sources & evidence

ORD record
ord-da6382b2cd2c4e1dae0ccf9ea29e1707
Source dataset
uspto-grants-2006_09
Patent number
US07112679B2

Reaction notes

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