Hydrochloric Acid → Methyl 2-amino-5-cyanobenzoate

HRID 2053455Notes

Reaction equation

HRID 2053455 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8](Br)[CH:7]=[CH:6][C:5]=1[NH2:11].[C:13]([Cu])#[N:14].Cl.CCOC(C)=O>CN1C(=O)CCC1.O>[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[C:8]([C:13]#[N:14])[CH:7]=[CH:6][C:5]=1[NH2:11]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 736224Methyl 2-amino-5-bromobenzoateHCID 178418546HCID 178418546, compound

Product 1

HCID 10058039Methyl 2-amino-5-cyanobenzoateYield 85%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

A mixture of 2-amino-5-bromo-benzoic acid methyl ester (5.00 g, 21.7 mmol) and CuCN (2.34 g, 26.1 mmol, 2.0 M) in 25 ml of NMP was stirred at reflux for 5 h, then cooled to rt. The mixture was poured into a solution of hydrated FeCl3 (15 g of FeCl3.6H2O) and conc. HCl (2.2 ml) in 15 ml of H2O. The resulting mixture was stirred at 60° C. for 1 h, cooled to rt. Treated with 200 ml of EtOAc, the mixture was washed with H2O (40 ml), 1N NaOH (3×30 ml), brine (30 ml) and dried (Na2SO4). Removal of the solvent under reduced pressure gave a slightly dark solid. Recrystalization of the solid in hexanes/DCM/EtOAc yielded 3.25 g (85%) of product as a yellow solid: 1H-NMR (CDCl3; 400 MHz) δ 8.20 (d, 1H, J=1.9 Hz), 7.45 (dd, 1H, J=8.9, 1.9 Hz), 6.67 (d, 1H, J=8.9 Hz), 6.29 (br s, 2H), 3.90 (s, 3H). Mass spectrum (ESI, m/z): Calcd. for C9H8N2O2, 177.1 (M+H), found 177.2.

Workup

  1. temperatureat reflux for 5 h
  2. stirringThe resulting mixture was stirred at 60° C. for 1 h
  3. temperaturecooled to rt
  4. washthe mixture was washed with H2O (40 ml), 1N NaOH (3×30 ml), brine (30 ml)
  5. dry with materialdried (Na2SO4)
  6. customRemoval of the solvent under reduced pressure
  7. customgave a slightly dark solid
  8. customRecrystalization of the solid in hexanes/DCM/EtOAc

Sources & evidence

ORD record
ord-2a369b49912b412ba0786cf47336c919
Source dataset
uspto-grants-2008_02
Patent number
US07326788B2

Reaction notes

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