Methyl 2-amino-5-bromobenzoate → Methyl 2-amino-5-cyanobenzoate

HRID 1519253Notes

Reaction equation

HRID 1519253 reaction equation
[Cu][C:2]#[N:3].[NH2:4][C:5]1[CH:14]=[CH:13][C:12](Br)=[CH:11][C:6]=1[C:7]([O:9][CH3:10])=[O:8]>CN1CCCC1=O.C(N)CN>[CH3:10][O:9][C:7](=[O:8])[C:6]1[CH:11]=[C:12]([C:2]#[N:3])[CH:13]=[CH:14][C:5]=1[NH2:4]

Participants

5

Reactant 2

HCID 736224Methyl 2-amino-5-bromobenzoateHCID 178418546HCID 178418546, compound

Product 1

HCID 10058039Methyl 2-amino-5-cyanobenzoateYield 73%

Reagents, catalysts & solvents 2

HCID 3301EthylenediamineSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
180 °C

Procedure

Copper(I) cyanide (available from Alfa Aesar; 10.71 g, 0.12 mol) was added to a stirred solution of methyl 2-amino-5-bromobenzoate (available from Aldrich Chemical Company, Inc.; 25.0 g, 0.11 mol) in N-methyl-2-pyrrolidone (50 mL) and the mixture was stirred at 180° C. for 4 h. The reaction mixture was cooled to room temperature, diluted with aqueous ethylenediamine (water:ethylenediamine=1:1; 250 mL), and filtered through pad of Celite. The filtrate was extracted with EtOAc (3×100 mL), and the combined organic layers were washed with water (100 mL) and brine (100 mL), dried over sodium sulfate, filtered, evaporated under reduced pressure, and purified by silica gel chromatography (100-200 mesh), using 5-10% ethyl acetate/hexanes as eluent, to give 2-amino-5-cyanobenzoic acid methyl ester (14.0 g, 73%) as a yellow powder. 1H NMR (400 MHz, DMSO-d6) δ 8.05 (d, J=1.9 Hz, 1H), 7.57 (dd, J=1.9, 8.8 Hz, 1H), 7.44 (br s, 2H), 6.88 (d, J=8.8 Hz, 1H), 3.81 (s, 3H).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. filtrationfiltered through pad of Celite
  3. extractionThe filtrate was extracted with EtOAc (3×100 mL)
  4. washthe combined organic layers were washed with water (100 mL) and brine (100 mL)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. custompurified by silica gel chromatography (100-200 mesh)

Sources & evidence

ORD record
ord-8a3e443f30094c5a883c2196bc1af286
Source dataset
uspto-grants-2015_07
Patent number
US09073881B2

Reaction notes

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