Citric Acid → Tert-butyl 4-(2-fluorophenyl)-2-(5-phenylpyridine-3-carboxamido)benzoate

HRID 454758Notes

Reaction equation

HRID 454758 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1B(O)O.Br[C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])=[C:20]([NH:31][C:32]([C:34]2[CH:35]=[N:36][CH:37]=[C:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH:39]=2)=[O:33])[CH:19]=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.C1(C)C=CC=CC=1.O.C(O)C>[F:7][C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[C:18]1[CH:30]=[CH:29][C:21]([C:22]([O:24][C:25]([CH3:27])([CH3:26])[CH3:28])=[O:23])=[C:20]([NH:31][C:32]([C:34]2[CH:35]=[N:36][CH:37]=[C:38]([C:40]3[CH:45]=[CH:44][CH:43]=[CH:42][CH:41]=3)[CH:39]=2)=[O:33])[CH:19]=1

Participants

10

Reactant 4

HCID 311Citric AcidHCID 10340Sodium CarbonateHCID 27343542-Fluorophenylboronic acidHCID 58508430Tert-butyl 4-bromo-2-(5-phenylpyridine-3-carboxamido)benzoate

Product 1

HCID 58508706Tert-butyl 4-(2-fluorophenyl)-2-(5-phenylpyridine-3-carboxamido)benzoate

Reagents, catalysts & solvents 5

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Ethanol (0.62 mL), water (0.31 mL), sodium carbonate (70 mg), 2-fluorophenylboronic acid (37 mg), and tetrakis(triphenylphosphine)palladium(0) (13 mg) were added to a toluene (2.1 mL) suspension 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 and 30 minutes. 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 [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 91-85% hexane/ethyl acetate] to obtain tert-butyl 4-(2-fluorophenyl)-2-(5-phenylpyridine-3-carboxamido)benzoate.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 2 hours and 30 minutes
  3. customThe organic layer was separated
  4. washwashed with a saturated aqueous solution of sodium chloride
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography [Fuji Silysia Chemical Ltd., PSQ100B (spherical), eluent: 91-85% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-049fe020f09f4c53ac73ee13db4e4642
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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