Potassium Cyanide → Methyl 4-bromo-2-cyanobenzoate

HRID 2173224Notes

Reaction equation

HRID 2173224 reaction equation
N[C:2]1[CH:11]=[C:10]([Br:12])[CH:9]=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].N([O-])=O.[Na+].C([O-])(O)=O.[Na+].[C-]#N.[K+].[C:25]([Cu])#[N:26]>Cl.O.[O-]S([O-])(=O)=O.[Cu+2].CCOC(C)=O.C1(C)C=CC=CC=1>[Br:12][C:10]1[CH:9]=[CH:8][C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([C:25]#[N:26])[CH:11]=1

Participants

11

Reactant 5

HCID 9032Potassium CyanideHCID 516892Sodium BicarbonateHCID 17871390Methyl 2-Amino-4-bromobenzoateHCID 23668193Sodium NitriteHCID 178418546HCID 178418546, compound

Product 1

HCID 58484706Methyl 4-bromo-2-cyanobenzoate

Reagents, catalysts & solvents 5

HCID 24462Copper SulfateCatalystHCID 313Hydrochloric AcidSolventHCID 962WaterSolvent4×HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of methyl 2-amino-4-bromobenzoate (500 mg, 2.2 mmol) in 2 mL of conc. HCl was added 5 mL of water and a solution of NaNO2 (159 mg, 2.3 mmol) in water (1 mL) was added over a 10-minute period at 0° C. This diazonium solution was then brought to pH 6 with aqueous NaHCO3. In a separated vail, a solution of CuSO4 (660 mg, 2.75 mmol) in water (2 mL) was added dropwise to a solution of KCN (657 mg, 10.11 mmol) in water (2 mL) at 0° C., then toluene (5 mL) was added and the mixture was stirred and heated to 60° C. The previously prepared diazonium solution was added dropwise to the brown CuCN solution at 60° C. over 40 min. The reaction mixture was heated to 70° C. for 1 hour and cooled to room temperature, and EtOAc (100 mL) was added. The organic phase was washed with brine (20 mL) and concentrated. The crude product was purified via cprep-TLC to afford the methyl 4-bromo-2-cyanobenzoate. 1H-NMR (400 MHz, CDCl3) δ 7.75-7.95 (m, 3H), 3.93 (s, 3H).

Workup

  1. temperatureThe reaction mixture was heated to 70° C. for 1 hour
  2. temperaturecooled to room temperature
  3. washThe organic phase was washed with brine (20 mL)
  4. concentrationconcentrated
  5. customThe crude product was purified via cprep-TLC

Sources & evidence

ORD record
ord-190b38edf56549b5b2d4643cab17e340
Source dataset
uspto-grants-2015_06
Patent number
US09056859B2

Reaction notes

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