Hydrochloric Acid → 2-Methyl-4-((2-methylbenzoyl)amino)benzoic acid

HRID 1886976Notes

Reaction equation

HRID 1886976 reaction equation
[Cl-].[CH3:2][C:3]1[CH:8]=[C:7]([NH:9][C:10](=[O:18])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH3:17])[CH:6]=[CH:5][C:4]=1[C:19](=[O:27])C[N+]1C=CC=CC=1.[Cl-].CC1C=CC(C(=[O:44])C[N+]2C=CC=CC=2)=C(NC(=O)C2C=CC=CC=2C)C=1.[OH-].[Na+].Cl>CO.O>[CH3:2][C:3]1[CH:8]=[C:7]([NH:9][C:10](=[O:18])[C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH3:17])[CH:6]=[CH:5][C:4]=1[C:19]([OH:27])=[O:44]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 866369041-{2-[2-Methyl-4-(2-methylbenzoylamino)phenyl]-2-oxoethyl}pyridinium chlorideHCID 866369061-{2-[4-Methyl-2-(2-methylbenzoylamino)phenyl]-2-oxoethyl}pyridinium chloride

Product 1

HCID 251921172-Methyl-4-((2-methylbenzoyl)amino)benzoic acidYield 60.5%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Conditions

Temperature
68 °C

Procedure

The isomer mixture of 1-{2-[2-methyl-4-(2-methylbenzoylamino)-phenyl]-2-oxoethyl}pyridinium chloride and 1-{2-[4-methyl-2-(2-methylbenzoylamino)phenyl]-2-oxoethyl}pyridinium chloride obtained in the above Reference Example 6 (207.3 g, 0.544 mole) is suspended in methanol (0.4 L) and thereto is added a solution of sodium hydroxide (52.5 g, 1.31 mole) in water (0.6 L), and the mixture is stirred at 60-76° C. for about 4 hours to complete the reaction. To the reaction mixture is added concentrated hydrochloric acid (0.108 L) at the same temperature to adjust pH=1. The mixture is stirred under ice cooling for one hour, and the precipitated crystals are separated by filtration. The resulting crystals are washed with water and dried at around 60° C. to give the crude product (125.5 g, yield 85.6%). A part of this crude product (20 g) is recrystallized from methanol (340 mL) and dried at 60° C. to give the desired product (12.1 g, yield 60.5%, purity by HPLC 99.7%).

Workup

  1. customthe reaction
  2. stirringThe mixture is stirred under ice cooling for one hour
  3. customthe precipitated crystals are separated by filtration
  4. washThe resulting crystals are washed with water
  5. customdried at around 60° C.
  6. customto give the crude product (125.5 g, yield 85.6%)
  7. customA part of this crude product (20 g) is recrystallized from methanol (340 mL)
  8. customdried at 60° C.

Sources & evidence

ORD record
ord-653f1e8f28664474a267d57ac67f9cc4
Source dataset
uspto-grants-2013_08
Patent number
US08501730B2

Reaction notes

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