Sodium Carbonate → 4,5-dibromo-2-(4-fluorophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole

HRID 538406Notes

Reaction equation

HRID 538406 reaction equation
Br[C:2]1[N:3]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[C:4]([Br:8])=[C:5]([Br:7])[N:6]=1.[F:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1.C([O-])([O-])=O.[Na+].[Na+]>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.COCCOC>[Br:7][C:5]1[N:6]=[C:2]([C:21]2[CH:22]=[CH:23][C:18]([F:17])=[CH:19][CH:20]=2)[N:3]([CH2:9][O:10][CH2:11][CH2:12][Si:13]([CH3:16])([CH3:15])[CH3:14])[C:4]=1[Br:8]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 109062032,4,5-tribromo-1-[[2-(trimethylsilyl)ethoxy]methyl]-1H-Imidazole

Product 1

HCID 185159564,5-dibromo-2-(4-fluorophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazoleYield 87%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
110 °C

Procedure

A microwave vial was charged with 2,4,5-tribromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (881 mg, 2.0 mmol, Example 2, Step 2), 4-fluorophenyl boronic acid (308 mg, 2.2 mmol), aqueous Na2CO3 solution (6 ml, 2.0 M, 12.0 mmol) and DME (12 ml). The mixture was sparged with argon for 15 min, followed by addition of Pd(PPh3)4 (120 mg, 0.1 mmol). The reaction vial was sealed and heated at 110° C. for 20 minutes in a microwave reactor; the reaction was deemed complete by LCMS. The reaction mixture was partitioned between saturated Na2CO3 solution and EtOAc (10 ml/30 ml), the organic layer was separated, washed with brine (10 ml), dried (Na2SO4), and concentrated. The resulting residue was purified by flash column chromatography (SiO2; 100:0-80:20 hexanes-EtOAc) to furnish 4,5-dibromo-2-(4-fluorophenyl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole (780 mg, 1.73 mmol, 87%) as a solid: 1H NMR (400 MHz, DMSO-d6) δ 7.80-7.70 (m, 2H), 7.37 (app t, J=9.0 Hz, 2H), 5.33 (s, 2H), 3.52 (t, J=8.2 Hz, 2H), 0.83 (t, J=8.2 Hz, 2H), −0.06 (s, 9H).

Workup

  1. customThe mixture was sparged with argon for 15 min
  2. customThe reaction
  3. customvial was sealed
  4. customThe reaction mixture was partitioned between saturated Na2CO3 solution and EtOAc (10 ml/30 ml)
  5. customthe organic layer was separated
  6. washwashed with brine (10 ml)
  7. dry with materialdried (Na2SO4)
  8. concentrationconcentrated
  9. customThe resulting residue was purified by flash column chromatography (SiO2; 100:0-80:20 hexanes-EtOAc)

Sources & evidence

ORD record
ord-585989d3d8284b6b85f15fab2e8da15c
Source dataset
uspto-grants-2014_10
Patent number
US08865732B2

Reaction notes

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