Potassium Phosphate, Tribasic → [5-(4-Fluoro-phenyl)-2-(3-hexyl-phenyl)-3-methyl-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

HRID 545370Notes

Reaction equation

HRID 545370 reaction equation
[CH2:1]([C:7]1[CH:8]=[C:9]([C:13]2[N:17]([CH3:18])[C:16]([C:19]([N:21]3[CH2:26][CH2:25][CH:24]([N:27]4[CH2:31][CH2:30][CH2:29][CH2:28]4)[CH2:23][CH2:22]3)=[O:20])=[C:15](I)[N:14]=2)[CH:10]=[CH:11][CH:12]=1)[CH2:2][CH2:3][CH2:4][CH2:5][CH3:6].[F:33][C:34]1[CH:39]=[CH:38][C:37](B(O)O)=[CH:36][CH:35]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:33][C:34]1[CH:39]=[CH:38][C:37]([C:15]2[N:14]=[C:13]([C:9]3[CH:10]=[CH:11][CH:12]=[C:7]([CH2:1][CH2:2][CH2:3][CH2:4][CH2:5][CH3:6])[CH:8]=3)[N:17]([CH3:18])[C:16]=2[C:19]([N:21]2[CH2:22][CH2:23][CH:24]([N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[CH2:25][CH2:26]2)=[O:20])=[CH:36][CH:35]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2856454-Fluorophenylboronic acidHCID 57541122[2-(3-Hexyl-phenyl)-5-iodo-3-methyl-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone

Product 1

HCID 57541079[5-(4-Fluoro-phenyl)-2-(3-hexyl-phenyl)-3-methyl-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanoneYield 77.4%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 0.275 g (0.50 mmol) of [2-(3-hexyl-phenyl)-5-iodo-3-methyl-3H-imidazol-4-yl]-(4-pyrrolidin-1-yl-piperidin-1-yl)-methanone (example 2) and 0.140 g (1.0 mmol) of 4-fluorophenyl boronic acid in 10 ml of DMF was added drop by drop 2.50 ml of tribasic potassium phosphate (2 M in water), followed by 0.029 g (0.025 mmol) of tetrakis-(triphenylphosphine)-palladium. This reaction mixture was stirred at 80° C. for two hours and subsequently cooled down to RT, then poured into crashed ice and extracted three times with CH2Cl2; the organic phases were washed with water, dried over magnesium sulfate, filtered and evaporated. The residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1) to give 0.20 g (76%) of the title compound as light yellow oil. MS: 517.4 (MH+).

Workup

  1. temperaturesubsequently cooled down to RT
  2. additionpoured
  3. extractionextracted three times with CH2Cl2
  4. washthe organic phases were washed with water
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by flash column chromatography (CH2Cl2/MeOH 1:0 to 9:1)

Sources & evidence

ORD record
ord-35ffed2589454e2493d2e48c07b99203
Source dataset
uspto-grants-2011_05
Patent number
US07935707B2

Reaction notes

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