Sodium Hydroxide → HCID 21847947, compound

HRID 618733Notes

Reaction equation

HRID 618733 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:9]=[C:10]([C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)[NH:11][C:12]=2[C:13]2[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=2)=[CH:4][CH:3]=1.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][C:31](B(O)O)=[CH:30][CH:29]=1.[OH-].[Na+]>C(O)C.C1(C)C=CC=CC=1.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>[Cl:25][C:22]1[CH:23]=[CH:24][C:19]([C:10]2[NH:11][C:12]([C:13]3[CH:18]=[CH:17][N:16]=[CH:15][CH:14]=3)=[C:8]([C:5]3[CH:6]=[CH:7][C:2]([C:31]4[CH:32]=[CH:33][C:28]([O:27][CH3:26])=[CH:29][CH:30]=4)=[CH:3][CH:4]=3)[N:9]=2)=[CH:20][CH:21]=1

Participants

7

Reactant 3

HCID 14798Sodium HydroxideHCID 201262(4-Methoxyphenyl)boronic acidHCID 21847944HCID 21847944, compound

Product 1

HCID 21847947HCID 21847947, compoundYield 25%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 60 mg (0.146 mmol) of 4-(4-bromophenyl)-2-(4-chlorophenyl)-5-(4-pyridyl)imidazole (from Step C) in 1 mL of ethanol and 1.5 mL of toluene was added 56 mg (0.365 mmol) of 4-methoxybenzeneboronic acid, followed by 0.73 mmol (584 μL of a 1.25 N solution) of aqueous NaOH, and 17 mg (0.146 mmol) of tetrakis(triphenylphosphine)palladium(0). The resulting reaction mixture was stirred at 90° C. overnight. After being cooled to room temperature, the reaction was quenched by addition of water and extracted with ethyl acetate twice. The organic layers were combined, washed with water and brine, and dried over sodium sulfate. After filtration and removal of volatiles, the crude product was flash chromatographed over silica gel (gradient elution using 20-50% EtOAc in hexane). This material appeared to be homogeneous by TLC but contained some uncoupled material as shown by HPLC trace. Therefore, it was further purified via a chromatotron, eluting slowly using a 5:95:0.5 mixture of methanol/DCM/HOAc to provide 16 mg of the desired product as a pale yellow solid, homogeneous by TLC, mass spectrum (CI) m/e 438 (M+1)+.

Workup

  1. customThe resulting reaction mixture
  2. temperatureAfter being cooled to room temperature
  3. customthe reaction was quenched by addition of water
  4. extractionextracted with ethyl acetate twice
  5. washwashed with water and brine
  6. dry with materialdried over sodium sulfate
  7. filtrationAfter filtration and removal of volatiles
  8. customchromatographed over silica gel (gradient elution using 20-50% EtOAc in hexane)
  9. customTherefore, it was further purified via a chromatotron
  10. washeluting slowly
  11. additiona 5:95:0.5 mixture of methanol/DCM/HOAc

Sources & evidence

ORD record
ord-52d7a999640f4f71abea8209b804fe3c
Source dataset
uspto-grants-1999_09
Patent number
US05955480

Reaction notes

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