Citric Acid → tert-butyl 4-(1-methyl-1H-pyrrol-2-yl)-2-(5-phenylpyridine-3-carboxamido)benzoate

HRID 454761Notes

Reaction equation

HRID 454761 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[CH3:7][N:8]1[CH:12]=[CH:11][CH:10]=[C:9]1B1OC(C)(C)C(C)(C)O1.Br[C:23]1[CH:35]=[CH:34][C:26]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])=[C:25]([NH:36][C:37]([C:39]2[CH:40]=[N:41][CH:42]=[C:43]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[CH:44]=2)=[O:38])[CH:24]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>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.C(OCC)(=O)C.O.C(O)C.C1(C)C=CC=CC=1>[CH3:7][N:8]1[CH:12]=[CH:11][CH:10]=[C:9]1[C:23]1[CH:35]=[CH:34][C:26]([C:27]([O:29][C:30]([CH3:32])([CH3:31])[CH3:33])=[O:28])=[C:25]([NH:36][C:37]([C:39]2[CH:40]=[N:41][CH:42]=[C:43]([C:45]3[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=3)[CH:44]=2)=[O:38])[CH:24]=1

Participants

10

Reactant 4

HCID 311Citric AcidHCID 10340Sodium Carbonate2×HCID 441187731-Methyl-1H-pyrrole-2-boronic acid, pinacol ester2×HCID 58508430Tert-butyl 4-bromo-2-(5-phenylpyridine-3-carboxamido)benzoate

Product 1

HCID 58508465tert-butyl 4-(1-methyl-1H-pyrrol-2-yl)-2-(5-phenylpyridine-3-carboxamido)benzoateYield 71%

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 702EthanolSolvent2×HCID 962WaterSolvent2×HCID 1140TolueneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Ethanol (0.62 mL), water (0.31 mL), sodium carbonate (70 mg), 1-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole (55 mg), and tetrakis(triphenylphosphine)palladium(0) (13 mg) were added to a toluene (2.1 mL) solution of tert-butyl 4-bromo-2-(5-phenylpyridine-3-carboxamido)benzoate (0.10 g), followed by heating to reflux under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and then sodium carbonate (23 mg), 1-methyl-2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrole (46 mg), and tetrakis(triphenylphosphine)palladium(0) (13 mg) were added thereto, followed by heating to reflux under a nitrogen atmosphere for 3 hours and 30 minutes. The reaction mixture was cooled to room temperature, and then toluene (1.0 mL), ethanol (0.31 mL), and water (0.16 mL) were added thereto, followed by heating to reflux under a nitrogen atmosphere for 2 hours. The reaction mixture was cooled to room temperature, and then a 10% aqueous solution of citric acid and ethyl acetate were added thereto. The organic layer was separated, washed with a saturated aqueous solution of sodium chloride, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by silica gel column chromatography [eluent: 95-85% hexane/ethyl acetate] to obtain 71 mg of tert-butyl 4-(1-methyl-1H-pyrrol-2-yl)-2-(5-phenylpyridine-3-carboxamido)benzoate as a light yellow solid.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 2 hours
  3. temperatureby heating
  4. temperatureto reflux under a nitrogen atmosphere for 3 hours and 30 minutes
  5. temperatureThe reaction mixture was cooled to room temperature
  6. temperatureby heating
  7. temperatureto reflux under a nitrogen atmosphere for 2 hours
  8. temperatureThe reaction mixture was cooled to room temperature
  9. customThe organic layer was separated
  10. washwashed with a saturated aqueous solution of sodium chloride
  11. dry with materialdried over anhydrous magnesium sulfate
  12. customthe solvent was evaporated under reduced pressure
  13. customThe obtained residue was purified by silica gel column chromatography [eluent: 95-85% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-260e35c9b211467fbe7aa23d3ad099ed
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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