Triethylamine → 2-Chloro-4-[[(3,5-dimethoxybenzyl)amino]carbonyl]benzoic acid, methyl ester

HRID 2270849Notes

Reaction equation

HRID 2270849 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:15]=[CH:16][C:17]=1[C:18]([O:20][CH3:21])=[O:19])[C:5]([O:7]N1C(=O)CCC1=O)=O.[CH3:22][O:23][C:24]1[CH:25]=[C:26]([CH:29]=[C:30]([O:32][CH3:33])[CH:31]=1)[CH2:27][NH2:28].C(N(CC)CC)C>CN(C)C=O>[Cl:1][C:2]1[CH:3]=[C:4]([C:5]([NH:28][CH2:27][C:26]2[CH:29]=[C:30]([O:32][CH3:33])[CH:31]=[C:24]([O:23][CH3:22])[CH:25]=2)=[O:7])[CH:15]=[CH:16][C:17]=1[C:18]([O:20][CH3:21])=[O:19]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 420973(3,5-Dimethoxyphenyl)methanamineHCID 235607681-[[3-Chloro-4-(methoxycarbonyl)benzoyl]oxy]-2,5-pyrrolidinedione

Product 1

HCID 865851482-Chloro-4-[[(3,5-dimethoxybenzyl)amino]carbonyl]benzoic acid, methyl esterYield 72.6%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A solution of 1-[[3-chloro-4-(methoxycarbonyl)benzoyl]oxy]-2,5-pyrrolidinedione (Example 5; 2.00 g, 6.4 mmol), 3,5-dimethoxybenzylamine (1.25 g, 7.5 mmol) and triethylamine (1.00 g, 9.9 mmol) in N,N-dimethylformamide (100 mL) was stirred at room temperature overnight. The solvent was evaporated (<0.5 mm Hg, 40° C.), ethyl acetate (200 mL) was added, and the solution was allowed to stand over the weekend at room temperature. The white solid was filtered off and discarded. Silica gel was added, the solvent was evaporated and the residue was chromatographed (30-50% ethyl acetate/hexanes) to give 2-chloro-4-[[[(3,5-dimethoxyphenyl) methyl]amino]carbonyl]benzoic acid, methyl ester (1.69 g, 72%) as a white solid, mp 101-103° C.

Workup

  1. customThe solvent was evaporated (<0.5 mm Hg, 40° C.), ethyl acetate (200 mL)
  2. additionwas added
  3. customto stand over the weekend at room temperature
  4. filtrationThe white solid was filtered off
  5. additionSilica gel was added
  6. customthe solvent was evaporated
  7. customthe residue was chromatographed (30-50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-565ac2d0bc3448a5af6755da8148eb23
Source dataset
uspto-grants-2001_12
Patent number
US06331640B1

Reaction notes

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