Citric Acid → Tert-butyl 4-(4-((tert-butoxycarbonyl)(methyl)amino)phenyl)-2-(5-phenylpyridine-3-carboxamido)benzoate

HRID 454768

Reaction equation

HRID 454768 reaction equation
C(=O)([O-])[O-].[Na+].[Na+].[CH3:7][N:8]([C:16]1[CH:21]=[CH:20][C:19](B2OC(C)(C)C(C)(C)O2)=[CH:18][CH:17]=1)[C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12].Br[C:32]1[CH:44]=[CH:43][C:35]([C:36]([O:38][C:39]([CH3:42])([CH3:41])[CH3:40])=[O:37])=[C:34]([NH:45][C:46]([C:48]2[CH:49]=[N:50][CH:51]=[C:52]([C:54]3[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=3)[CH:53]=2)=[O:47])[CH:33]=1.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C.COCCOC.O>[C:11]([O:10][C:9]([N:8]([CH3:7])[C:16]1[CH:17]=[CH:18][C:19]([C:32]2[CH:44]=[CH:43][C:35]([C:36]([O:38][C:39]([CH3:41])([CH3:40])[CH3:42])=[O:37])=[C:34]([NH:45][C:46]([C:48]3[CH:49]=[N:50][CH:51]=[C:52]([C:54]4[CH:59]=[CH:58][CH:57]=[CH:56][CH:55]=4)[CH:53]=3)=[O:47])[CH:33]=2)=[CH:20][CH:21]=1)=[O:15])([CH3:12])([CH3:13])[CH3:14]

Participants

9

Reactant 4

HCID 311Citric AcidHCID 10340Sodium CarbonateHCID 4712653tert-Butyl methyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamateHCID 58508430Tert-butyl 4-bromo-2-(5-phenylpyridine-3-carboxamido)benzoate

Product 1

HCID 66990300Tert-butyl 4-(4-((tert-butoxycarbonyl)(methyl)amino)phenyl)-2-(5-phenylpyridine-3-carboxamido)benzoateYield 83.4%

Reagents, catalysts & solvents 4

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

Water (0.60 mL), sodium carbonate (88 mg), tert-butyl methyl(4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)carbamate (0.13 g), and bis(triphenylphosphine)palladium(II) dichloride (5.0 mg) were added to an ethylene glycol dimethyl ether (2.0 mL) solution of tert-butyl 4-bromo-2-(5-phenylpyridine-3-carboxamido)benzoate (0.15 g), followed by heating to reflux under a nitrogen atmosphere for 1 hour. 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 0.16 g of tert-butyl 4-(4-((tert-butoxycarbonyl)(methyl)amino)phenyl)-2-(5-phenylpyridine-3-carboxamido)benzoate as a white solid.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 1 hour
  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 [eluent: 95-85% hexane/ethyl acetate]

Sources & evidence

ORD record
ord-66c81f6e2ef04674afc77253705b5802
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Linked notes

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