Trimethyl borate → 2-(Benzyloxy)-4-methoxyphenylboronic acid

HRID 1857094Notes

Reaction equation

HRID 1857094 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH3:9])=[CH:4][C:3]=1[O:10][CH2:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.[Mg].[B:19](OC)([O:22]C)[O:20]C>BrCCBr.C1COCC1>[CH3:9][O:8][C:5]1[CH:6]=[CH:7][C:2]([B:19]([OH:22])[OH:20])=[C:3]([O:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[CH:4]=1

Participants

6

Reactant 3

HCID 8470Trimethyl borateHCID 5462224MagnesiumHCID 184340291-Bromo-4-methoxy-2-phenylmethoxybenzene

Product 1

HCID 118320852-(Benzyloxy)-4-methoxyphenylboronic acidYield 85%

Reagents, catalysts & solvents 2

HCID 78391,2-DibromoethaneCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

A 2 L three-necked flask equipped with thermometer, reflux condenser and mechanical stirrer was charged with 1-bromo-4-methoxy-2-(phenylmethoxy)benzene (43.0 g, 0.147 mol), anhydrous THF (600 mL) under nitrogen. Magnesium turnings (4.2 g, 0.17 mol) and 1,2-dibromoethane (0.5 mL, 6 mmol) was then added and the mixture heated to reflux. After 1.5 h, the reaction was cooled to -78° C. and B(OMe)3 (33.4 mL, 0.294 mol) added dropwise while maintaining an internal temperature below -60° C. Upon complete addition, the reaction was quenched with 5% HCl (15 mL) to pH=3.0, portioned with EtOAc (100 mL), the organic phase separated, washed with brine (100 mL), dried (MgSO4) and concentrated in vacuo giving a pale yellow solid. The solid was triturated with hexane (90 mL), filtered and dried to afford [4-methoxy-2(phenylmethoxy)phenyl] boronic acid as a pale white solid (32 g, 85%): mp 127.0-129.0° C.; 1H NMR δ 7.8 (d, J=8.2 Hz, 1 H), 7.5-7.3 (m, 5 H), 6.6 (dd, J=8.2, 2.7 Hz, 1 H), 6.55 (d, J=2.7 Hz, 1 H), 5.65 (s, 2 H), 5.15 (s, 2 H), 3.85 (s, 3 H).

Workup

  1. customA 2 L three-necked flask equipped with thermometer
  2. temperaturereflux condenser and mechanical stirrer
  3. temperaturethe mixture heated to reflux
  4. temperaturewhile maintaining an internal temperature below -60° C
  5. additionUpon complete addition
  6. customthe reaction was quenched with 5% HCl (15 mL) to pH=3.0
  7. customthe organic phase separated
  8. washwashed with brine (100 mL)
  9. dry with materialdried (MgSO4)
  10. concentrationconcentrated in vacuo
  11. customgiving a pale yellow solid
  12. customThe solid was triturated with hexane (90 mL)
  13. filtrationfiltered
  14. customdried

Sources & evidence

ORD record
ord-2bcffca4ebcd43aca0bc352e2f6d429a
Source dataset
uspto-grants-2000_11
Patent number
US06143907

Reaction notes

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