Ethyl Acetate → Tert-butyl 2-(2-hydroxy-5-phenylbenzamido)-4-phenylbenzoate

HRID 454580Notes

Reaction equation

HRID 454580 reaction equation
[C:1]1(OB=O)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(=O)(O)[O-].[Na+].C([O:18][C:19]1[CH:46]=[CH:45][C:44](Br)=[CH:43][C:20]=1[C:21]([NH:23][C:24]1[CH:36]=[C:35]([C:37]2[CH:42]=CC=C[CH:38]=2)[CH:34]=[CH:33][C:25]=1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[O:22])(=O)C.[C:48](=O)([O-])[O-].[K+].[K+].C(O[CH2:58][CH3:59])(=O)C>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.O.COCCOC>[OH:18][C:19]1[CH:46]=[CH:45][C:44]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[CH:43][C:20]=1[C:21]([NH:23][C:24]1[CH:36]=[C:35]([C:37]2[CH:42]=[CH:59][CH:58]=[CH:48][CH:38]=2)[CH:34]=[CH:33][C:25]=1[C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])=[O:22]

Participants

9

Reactant 5

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 516892Sodium BicarbonateHCID 14438906HCID 14438906, compoundHCID 66990421Tert-butyl 2-(2-acetoxy-5-bromobenzamido)-4-phenylbenzoate

Product 1

HCID 58508748Tert-butyl 2-(2-hydroxy-5-phenylbenzamido)-4-phenylbenzoate

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

Ethylene glycol dimethyl ether (1.4 mL), water (0.42 mL), phenylboranic acid (0.045 g), sodium bicarbonate (0.063 g), and bis(triphenylphosphine)palladium(II) dichloride (4 mg) were added to tert-butyl 2-(2-acetoxy-5-bromobenzamido)-4-phenylbenzoate (0.15 g), followed by heating to reflux under a nitrogen atmosphere for 45 minutes. The reaction mixture was cooled to room temperature, and potassium carbonate (0.12 g) was added thereto, followed by stirring under a nitrogen atmosphere at room temperature for 2 hours. Water and ethyl acetate were added to the reaction mixture. 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. Methanol (2 mL), dioxane (4 mL), and a 2 mol/L aqueous solution of sodium hydroxide (1.5 mL) were added to the obtained residue, followed by stirring at room temperature for 1 hour and 40 minutes. The solvent was evaporated under reduced pressure, and 1 mol/L hydrochloric acid and ethyl acetate were added to the residue. 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 [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 95-80% hexane/ethyl acetate] and further purified by silica gel column chromatography [eluent: chloroform] to obtain 0.086 g of tert-butyl 2-(2-hydroxy-5-phenylbenzamido)-4-phenylbenzoate as a white solid.

Workup

  1. temperatureby heating
  2. temperatureto reflux under a nitrogen atmosphere for 45 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. additionMethanol (2 mL), dioxane (4 mL), and a 2 mol/L aqueous solution of sodium hydroxide (1.5 mL) were added to the obtained residue
  8. stirringby stirring at room temperature for 1 hour and 40 minutes
  9. customThe solvent was evaporated under reduced pressure, and 1 mol/L hydrochloric acid and ethyl acetate
  10. additionwere added to the residue
  11. customThe organic layer was separated
  12. washwashed with a saturated aqueous solution of sodium chloride
  13. dry with materialdried over anhydrous magnesium sulfate
  14. customthe solvent was evaporated under reduced pressure
  15. customThe obtained residue was purified by silica gel column chromatography [Kanto Chemical Co., Inc., silica gel 60 (spherical), eluent: 95-80% hexane/ethyl acetate]
  16. customfurther purified by silica gel column chromatography [eluent: chloroform]

Sources & evidence

ORD record
ord-54182d24095542eaaab58b1b1fc9458c
Source dataset
uspto-grants-2013_07
Patent number
US08492582B2

Reaction notes

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