Citric Acid → Methyl 2-amino-3-chloro-4-methoxybenzoate

HRID 880784Notes

Reaction equation

HRID 880784 reaction equation
[NH2:1][C:2]1[C:10]([Cl:11])=[C:9]([O:12][CH3:13])[CH:8]=[CH:7][C:3]=1[C:4]([OH:6])=[O:5].[C:14]([O-])([O-])=O.[K+].[K+].CI.C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C=O)C>[CH3:14][O:5][C:4](=[O:6])[C:3]1[CH:7]=[CH:8][C:9]([O:12][CH3:13])=[C:10]([Cl:11])[C:2]=1[NH2:1]

Participants

6

Reactant 4

HCID 311Citric AcidHCID 6328Methyl iodideHCID 11430Potassium CarbonateHCID 666505632-Amino-3-chloro-4-methoxybenzoic acid

Product 1

HCID 66650895Methyl 2-amino-3-chloro-4-methoxybenzoateYield 50%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a stirred solution of compound 247d (1.9 g, 9.6 mmol) in dry DMF (25 mL) was added K2CO3 (1.32 g, 9.6 mmol) at room temperature. The reaction mixture was stirred for 30 min and methyl iodide (0.77 mL, 12.4 mmol) was added. After 2 hrs at room temperature, 5% aqueous citric acid was added. The mixture was extracted with EtOAc. Organics were washed with water, dried over Na2SO4, filtered, concentrated under reduced pressure, and purified by chromatography on silica gel (petroleum ether/EtOAc) to yield compound 248d as beige solid in 50% yield. 1H NMR (CDCl3, 400 MHz) δ (ppm) 3.79 (s, 3H), 3.86 (s, 3H), 6.23 (d, J=9.03 Hz, 1H), 7.75 (d, J=9.03 Hz, 1H).

Workup

  1. waitAfter 2 hrs at room temperature
  2. extractionThe mixture was extracted with EtOAc
  3. washOrganics were washed with water
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. custompurified by chromatography on silica gel (petroleum ether/EtOAc)

Sources & evidence

ORD record
ord-ba316a8fc9184f07b3132f69534c8653
Source dataset
uspto-grants-2015_03
Patent number
US08993595B2

Reaction notes

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