Hydrochloric Acid → Ethyl 3-bromo-4-cyanobenzoate

HRID 1373690Notes

Reaction equation

HRID 1373690 reaction equation
Cl.N[C:3]1[CH:13]=[CH:12][C:6]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:5][C:4]=1[Br:14].N([O-])=O.[Na+].[C:19]([Cu])#[N:20].[C-]#N.[Na+]>O.CCOC(C)=O>[Br:14][C:4]1[CH:5]=[C:6]([CH:12]=[CH:13][C:3]=1[C:19]#[N:20])[C:7]([O:9][CH2:10][CH3:11])=[O:8]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8929Sodium CyanideHCID 242793Ethyl 4-amino-3-bromobenzoateHCID 23668193Sodium NitriteHCID 178418546HCID 178418546, compound

Product 1

HCID 18374323Ethyl 3-bromo-4-cyanobenzoate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
5 °C

Procedure

To a three necked 3 L round bottomed flask with a mechanical stirrer was added 3 M aqueous HCl (790 mL), followed by ethyl 4-amino-3-brombenzoate (195 g, 0.8 mol) and the mixture was stirred for 15 min. After cooling to 5° C., a solution of 4M aqueous NaNO2 (240 mL, 0.96 mol) was added over a period of 30–45 min. The resulting mixture was further stirred for 30 min. and an almost homogenous solution was obtained. The mixture was filtered through glass wool to remove the insoluble residue. The solution was then added to a vigorously stirred solution of CuCN (111 g, 1.24 mol) and NaCN (162 g, 3.3 mol) in H2O (1 L) and EtOAc (500 mL) at room temperature in a 6 L Erlenmeyer flask over ˜45 min. The resulting mixture was further stirred at r.t. for 30 min., filtered through celite and extracted with EtOAc. The EtOAc extract was washed with brine, 0.5 M aqueous NaOH, dried (MgSO4) and concentrated. Chromatography over silica gel and elution with hexanes:EtOAc (6:1), then (3:1), swished with hexanes and small amount of Et2O to give a light brown powder. The mother liquor was concentrated and swished again. Combined yield of the title compound was 119 g (58%).

Workup

  1. stirringThe resulting mixture was further stirred for 30 min.
  2. customan almost homogenous solution was obtained
  3. filtrationThe mixture was filtered through glass wool
  4. customto remove the insoluble residue
  5. stirringThe resulting mixture was further stirred at r.t. for 30 min.
  6. filtrationfiltered through celite
  7. extractionextracted with EtOAc
  8. extractionThe EtOAc extract
  9. washwas washed with brine, 0.5 M aqueous NaOH
  10. dry with materialdried (MgSO4)
  11. concentrationconcentrated
  12. washChromatography over silica gel and elution with hexanes:EtOAc (6:1)
  13. customto give a light brown powder
  14. concentrationThe mother liquor was concentrated

Sources & evidence

ORD record
ord-2332fed3a50a4dc1bdf690b05b888bc9
Source dataset
uspto-grants-2007_01
Patent number
US07163932B2

Reaction notes

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