3-Chlorobenzoic Acid → 3-(Methyl(phenyl)amino)benzoic acid

HRID 1354965Notes

Reaction equation

HRID 1354965 reaction equation
[OH-].[K+].Cl[C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([OH:9])=[O:8].[CH3:13][NH:14][C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>OS(O)(=O)=O.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].CC1C=CC(C(C2C=CC(C)=CC=2)C(=O)C(C)C)=CC=1.CC(O)(C)C>[CH3:13][N:14]([C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1)[C:4]1[CH:5]=[C:6]([CH:10]=[CH:11][CH:12]=1)[C:7]([OH:9])=[O:8]

Participants

8

Reactant 3

HCID 4473-Chlorobenzoic AcidHCID 7515N-MethylanilineHCID 14797Potassium Hydroxide

Product 1

HCID 211061273-(Methyl(phenyl)amino)benzoic acidYield 102.5%

Reagents, catalysts & solvents 4

HCID 1118Sulfuric AcidCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 120407443-Methyl-1,1-bis(4-methylphenyl)-2-butanoneCatalystHCID 6386tert-ButanolSolvent2×

Conditions

Temperature
100 °C

Procedure

An oven-dried resealable Schlenk flask was evacuated and backfilled with argon. The flask was charged with Pd2 dba3 (9.2 mg, 0.01 mmol, 2 mol % Pd), Ligand 1 (19 mg, 0.04 mmol, 4 mol %), pulverized KOH (168 mg, 3.0 mmol), and 3-chlorobenzoic acid (156 mg, 1.0 mmol). The flask was evacuated and backfilled with argon (3×) and then capped with a rubber septum. To the flask was added t-BuOH (2.0 mL), N-methyl-aniline (0.163 mL, 1.5 mmol) and t-BuOH (0.5 mL). The septum was replaced with a Teflon screwcap, the flask was sealed, and the mixture was heated to 100° C. with stirring until the starting aryl chloride was consumed by GC analysis (3 h, GC monitoring was conducted by diluting a small aliquot from the reaction with MeOH (1-2 mL), adding 2-3 drops H2SO4 and heating until 0.5 mL liquid was left, filtering through a small pipette silica plug and observing the disappearance of the corresponding methyl ester). The reaction was cooled to room temperature, diluted with 5% aq. NaOH and extracted with Et2O. The aqueous layer was cooled to 0° C. and acidified with HCl (12.0 M) until pH ˜4. The aqueous layer was extracted with Et2O, dried over anh. MgSO4, filtered, and concentrated under reduced pressure to give crude product (233 mg). The product was purified by recrystallizing in hot hexanes/chloroform (5:1) to give a light yellow solid (191 mg, 84%, ≧95% pure).

Workup

  1. customAn oven-dried resealable Schlenk flask was evacuated
  2. customThe flask was evacuated
  3. customcapped with a rubber septum
  4. customthe flask was sealed
  5. customwas consumed by GC analysis (3 h, GC monitoring
  6. additionby diluting a small aliquot
  7. customfrom the reaction with MeOH (1-2 mL)
  8. waitwas left
  9. filtrationfiltering through a small pipette silica plug
  10. temperatureThe reaction was cooled to room temperature
  11. additiondiluted with 5% aq. NaOH
  12. extractionextracted with Et2O
  13. temperatureThe aqueous layer was cooled to 0° C.
  14. extractionThe aqueous layer was extracted with Et2O
  15. dry with materialdried over anh. MgSO4
  16. filtrationfiltered
  17. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-83e378143f0f44c6a0ca9e89008b1042
Source dataset
uspto-grants-2007_05
Patent number
US07223879B2

Reaction notes

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