Water → HCID 86707751, compound

HRID 2410095Notes

Reaction equation

HRID 2410095 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[N:7]=[C:8](Br)[N:9]([CH:21]([CH3:23])[CH3:22])[C:10]=1[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=1[CH3:20])[OH:12])=[O:5])[CH3:2].O.[CH3:26][O:27][C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][C:29]=1B(O)O.C([O-])([O-])=O.[K+].[K+]>O1CCOCC1.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]([C:6]1[N:7]=[C:8]([C:29]2[CH:30]=[CH:31][CH:32]=[CH:33][C:28]=2[O:27][CH3:26])[N:9]([CH:21]([CH3:23])[CH3:22])[C:10]=1[CH:11]([C:13]1[CH:18]=[CH:17][C:16]([Cl:19])=[CH:15][C:14]=1[CH3:20])[OH:12])=[O:5])[CH3:2]

Participants

7

Reactant 4

HCID 962WaterHCID 11430Potassium CarbonateHCID 27339582-Methoxyphenylboronic acidHCID 86707752HCID 86707752, compound2×

Product 1

HCID 86707751HCID 86707751, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of 2-bromo-5-[(4-chloro-2-methyl-phenyl)-hydroxy-methyl]-1-isopropyl-1H-imidazole-4-carboxylic acid ethyl ester (intermediate C, 3.5 g, 8.4 mmol) in dioxane (80 ml)/H2O (20 ml) were added 2-methoxy-phenyl boronic acid (2.0 g, 13.2 mmol), K2CO3 (3 g, 21.7 mmol). The mixture was degassed for 5 min and then Pd(PPh3)4 (1.7 g, 1.5 mmol) was added. The mixture was stirred at 100° C. for 2 h to give a complete conversion. Dioxane was removed under reduced pressure. The residual material was dissolved in EtOAc and extracted with brine. The aqueous layer was washed with EtOAc. The combined organic layers were dried (Na2SO4), filtered and concentrated under reduced pressure. The product was fixed on silica gel and purified by flash chromatography (silica gel, solvent: CH2Cl2/EtOAc, 100:0→80:20) to give the title compound as a yellow foam. tR: 1.27 min (LC-MS 2); ESI-MS 433.3 [M+H]+ (LC-MS 2). 1H-NMR (DMSO-d6, 400 MHz) δ ppm 7.56-7.48 (m, 2H), 7.29-7.05 (m, 3H), 7.34-7.29 (m, 1H), 7.10-7.96 (m, 1H), 6.94-6.91 (m, 1H), 6.52 (d, 1H), 4.58-4.52 (m, 1H), 4.24 (q, 2H), 3.73/3.68 (s, 3H), 2.16 (s, 3H), 1.27 (t, 3H), 1.05 (d, 3H), 0.58 (d, 3H).

Workup

  1. customThe mixture was degassed for 5 min
  2. customto give a complete conversion
  3. customDioxane was removed under reduced pressure
  4. dissolutionThe residual material was dissolved in EtOAc
  5. extractionextracted with brine
  6. washThe aqueous layer was washed with EtOAc
  7. dry with materialThe combined organic layers were dried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. custompurified by flash chromatography (silica gel, solvent: CH2Cl2/EtOAc, 100:0→80:20)

Sources & evidence

ORD record
ord-0172dcfba3674af1ba9f95fd482f04a2
Source dataset
uspto-grants-2014_08
Patent number
US08815926B2

Reaction notes

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