1,2-Dimethoxyethane → 2-Bromo-4-(4-fluoro-benzyl)-1-methoxy-benzene

HRID 1632045Notes

Reaction equation

HRID 1632045 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([CH:7]=[CH:8][C:9]=1[O:10][CH3:11])[CH2:5]Br.[F:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+].C(COC)OC>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C>[Br:1][C:2]1[CH:3]=[C:4]([CH2:5][C:16]2[CH:17]=[CH:18][C:13]([F:12])=[CH:14][CH:15]=2)[CH:7]=[CH:8][C:9]=1[O:10][CH3:11]

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 62657Potassium Phosphate, TribasicHCID 2856454-Fluorophenylboronic acidHCID 112774622-Bromo-4-(bromomethyl)-1-methoxybenzene

Product 1

HCID 184121302-Bromo-4-(4-fluoro-benzyl)-1-methoxy-benzeneYield 40.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
60 °C

Procedure

In a 250 mL round-bottomed flask equipped with a stir bar was placed 3-bromo-4-methoxybenzyl bromide (5.0 g, 17.9 mmol), 4-fluorophenylboronic acid (2.76 g, 19.7 mmol), potassium phosphate (tribasic) (7.60 g, 35.8 mmol), dimethoxyethane (30 mL) and 50% aqueous ethanol (30 mL). The mixture was degassed with nitrogen for 30 minutes and then added tetrakis(triphenylphosphine)palladium(0) (5.17 g, 4.48 mmol). The mixture was heated to 60° C. for 4 hours and then the palladium catalyst was filtered off. To the filtrate were added water (100 mL) and a saturated ammonium chloride solution (150 mL). After extracting with ethyl acetate (3×100 mL), the organic portions were combined, washed with brine (150 mL), dried (MgSO4) and concentrated. The crude material was purified by column utilizing 5% EtOAc/hexanes as the eluent to produce 2.12 g of 2-bromo-4-(4-fluoro-benzyl)-1-methoxy-benzene as a colorless oil in 40% yield.

Workup

  1. customIn a 250 mL round-bottomed flask equipped with a stir bar
  2. customThe mixture was degassed with nitrogen for 30 minutes
  3. filtrationthe palladium catalyst was filtered off
  4. additionTo the filtrate were added water (100 mL)
  5. extractionAfter extracting with ethyl acetate (3×100 mL)
  6. washwashed with brine (150 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated
  9. customThe crude material was purified by column

Sources & evidence

ORD record
ord-fa4e84e4bbd4449180d893150bf4d260
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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