Methyl Anthranilate → Methyl 2-(3-chloro-4-methoxybenzamido)benzoate

HRID 2099969Notes

Reaction equation

HRID 2099969 reaction equation
[NH2:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[Cl:12][C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[C:16](O)=[O:17].CCN=C=NCCCN(C)C>CN(C=O)C.CN(C1C=CN=CC=1)C>[Cl:12][C:13]1[CH:14]=[C:15]([CH:19]=[CH:20][C:21]=1[O:22][CH3:23])[C:16]([NH:1][C:2]1[CH:11]=[CH:10][CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5])=[O:17]

Participants

6

Reactant 3

HCID 8635Methyl AnthranilateHCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 1699823-Chloro-p-anisic acid

Product 1

HCID 800035Methyl 2-(3-chloro-4-methoxybenzamido)benzoateYield 33.2%

Reagents, catalysts & solvents 2

HCID 142844-(Dimethylamino)pyridineCatalystHCID 6228DimethylformamideSolvent

Procedure

A solution of methyl 2-aminobenzoate (500 mg, 3.3 mmol) (Aldrich Chemical Co., Milwaukee, Wis.) and 3-chloro-4-methoxybenzoic acid (645 mg, 3.3 mmol) (Lancaster Synthesis Ltd., Windham, N.H.) in DMF (20 mL) was treated with EDCI (1.3 g, 6.6 mmol) and DMAP (800 mg, 6.6 mmol) at room temperature. The reaction mixture was stirred for 24 hours, and then concentrated. The crude residue was dissolved in EtOAc (50 mL) and washed with 0.1 N HCl (2×20 mL), saturated aqueous NaHCO3 (2×20 mL). The organic layer was dried (Na2SO4), filtered, and concentrated. The crude product was purified by chromatography (SiO2, 15% EtOAc in hexanes) to afford 42A as a white solid (350 mg, 33%).

Workup

  1. concentrationconcentrated
  2. dissolutionThe crude residue was dissolved in EtOAc (50 mL)
  3. washwashed with 0.1 N HCl (2×20 mL), saturated aqueous NaHCO3 (2×20 mL)
  4. dry with materialThe organic layer was dried (Na2SO4)
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe crude product was purified by chromatography (SiO2, 15% EtOAc in hexanes)

Sources & evidence

ORD record
ord-2ebb2b1e16f546d5ae3a5bb1b7b7de45
Source dataset
uspto-grants-2009_08
Patent number
US07569725B2

Reaction notes

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