Tetrahydrofuran → 2-(2,4-Difluorophenyl)-1-(3-ethoxyphenyl)-1H-imidazole-4-carboxylic acid

HRID 2356596Notes

Reaction equation

HRID 2356596 reaction equation
[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([NH:10][C:11]([C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[F:20])=[NH:12])[CH:7]=[CH:8][CH:9]=1)[CH3:2].C[Si]([N-][Si](C)(C)C)(C)C.[Na+].C([O:33][C:34]1C=C(C=[CH:39][CH:40]=1)N)C.FC1C=C(F)C=CC=1C#N.[O:51]1CCCC1>[Cl-].[Na+].O.ClCCl>[CH2:1]([O:3][C:4]1[CH:5]=[C:6]([N:10]2[CH:39]=[C:40]([C:34]([OH:33])=[O:51])[N:12]=[C:11]2[C:13]2[CH:18]=[CH:17][C:16]([F:19])=[CH:15][C:14]=2[F:20])[CH:7]=[CH:8][CH:9]=1)[CH3:2]

Participants

8

Reactant 5

HCID 8028TetrahydrofuranHCID 121203-EthoxyanilineHCID 775452,4-DifluorobenzonitrileHCID 2724254Sodium bis(trimethylsilyl)amideHCID 178466610HCID 178466610, compound

Product 1

HCID 534142232-(2,4-Difluorophenyl)-1-(3-ethoxyphenyl)-1H-imidazole-4-carboxylic acid

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
-78 °C

Procedure

N-(3-Ethoxyphenyl)-2,4-difluorobenzenecarboximidamide To a solution of 2.2 ml (4.4 mmol) of 2.0 M (in tetrahydrofuran) sodium bis(trimethylsilyl)amide in 10 mL of tetrahydrofuran at ambient temperature was added 0.52 mL (4.0 mmol) of 3-ethoxyaniline and the resulting solution was stirred for 20 min. The reaction mixture was cooled to −78° C. and then was added 0.57 ml (4.0 mmol) of 2,4-difluorobenzonitrile. The resulting mixture was stirred from −78° C. to ambient temperature for 5 hrs and then poured into brine (25 mL) and dichloromethane (50 mL). The organic layer was separated and the aqueous layer was extracted with dichloromethane (25 mL). The combined organic layers were dried over sodium sulfate, filtered and concentrated in vacuo. Flash chromatography on a Biotage Horizon® system (silica gel, 0 to 50% ethyl acetate in hexanes gradient) gave the title compound as a yellow oil. LC/MS 277.2 (M+1).

Workup

  1. stirringThe resulting mixture was stirred from −78° C. to ambient temperature for 5 hrs
  2. customThe organic layer was separated
  3. extractionthe aqueous layer was extracted with dichloromethane (25 mL)
  4. dry with materialThe combined organic layers were dried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-388353a10fa74a2a877748f71b739f27
Source dataset
uspto-grants-2010_07
Patent number
US07759352B2

Reaction notes

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