Imidazole → HCID 178466106, compound

HRID 2054914Notes

Reaction equation

HRID 2054914 reaction equation
[CH2:1]([O:3][C:4]1[C:9]([C:10]#[N:11])=[C:8]([F:12])[C:7](B2OC(C)(C)C(C)(C)O2)=[CH:6][CH:5]=1)[CH3:2].C([O-])([O-])=O.[Na+].[Na+].[NH:28]1[CH:32]=[CH:31][N:30]=[CH:29]1>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>[CH2:1]([O:3][C:4]1[C:9]([C:10]#[N:11])=[C:8]([F:12])[C:7]([C:32]2[N:28]=[CH:29][NH:30][CH:31]=2)=[CH:6][CH:5]=1)[CH3:2]

Participants

6

Reactant 3

HCID 795ImidazoleHCID 10340Sodium CarbonateHCID 59656645HCID 59656645, compound

Product 1

HCID 178466106HCID 178466106, compoundYield 46.1%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
85 °C

Procedure

To a sealed tube was added the above tert-butyl ester intermediate (25.5 mg, 0.103 mmol), 6-ethoxy-2-fluoro-3-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-benzonitrile (60 mg, 0.206 mmol) and tetrakis(triphenylphosphine)palladium(0) (23.85 mg, 0.0206 mmol) in 1 mL of dimethoxyethane, followed by the addition of 0.5 mL of 20% Na2CO3. The mixture was heated at 85° C. for 4 h. LCMS showed both de-boc and boc-protected imidazole compounds formed. The reaction mixture was filtered, concentrated and the residue was purified by silica gel chromatography eluting with 2-5% MeOH/CH2Cl2. The boc-protected intermediate was not found during the column process, the de-boc intermediate was found and the fractions were collected and concentrated to afford 11 mg (46.1%) of 6-ethoxy-2-fluoro-3-(1H-imidazol-4-yl)-benzonitrile.

Workup

  1. customformed
  2. filtrationThe reaction mixture was filtered
  3. concentrationconcentrated
  4. customthe residue was purified by silica gel chromatography
  5. washeluting with 2-5% MeOH/CH2Cl2
  6. customthe fractions were collected
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-af90764a81954a7e8bf27194c890bd8e
Source dataset
uspto-grants-2008_02
Patent number
US07329764B2

Reaction notes

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