Hydrochloric Acid → Methyl 3-bromo-4-iodobenzoate

HRID 1961537Notes

Reaction equation

HRID 1961537 reaction equation
[CH3:1][O:2][C:3](=[O:12])[C:4]1[CH:9]=[CH:8][C:7](N)=[C:6]([Br:11])[CH:5]=1.Cl.N([O-])=O.[Na+].[I-:18].[K+]>CC(C)=O.O>[Br:11][C:6]1[CH:5]=[C:4]([CH:9]=[CH:8][C:7]=1[I:18])[C:3]([O:2][CH3:1])=[O:12]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 4875Potassium IodideHCID 1515280Methyl 4-amino-3-bromobenzoateHCID 23668193Sodium Nitrite

Product 1

HCID 17750019Methyl 3-bromo-4-iodobenzoateYield 55%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent3×

Conditions

Temperature
0 °C

Procedure

A solution of 4-amino-3-bromo-benzoic acid methyl ester (5.0 g, 22.0 mmol from Aldrich) in acetone (35 mL) was treated with 6M HCl (35 mL). The solution was cooled to 0° C. and treated dropwise with NaNO2 (1.84 g, 26.1 mmol) dissolved in 10 mL water. After stirring for 2 hours at 0° C., the reaction was slowly treated with potassium iodide (5.47 g, 32.6 mmol) dissolved in 20 mL water. The reaction mixture was allowed to warm to room temperature and stir for 1 hour. Reaction mixture was diluted with water and extracted with EtOAc (2×150 mL). The combined organic phase was dried (Na2SO4) and concentrated under vacuum The residue was chromatographed (80 g Redi-Sep column) eluting from 100% heptane to 20:80 EtOAc:heptane to afford the intermediate (4.1 g, 55%) as a solid. 1HNMR (CDCl3): 8.27 (1H), 7.98 (1H), 7.64 (1H), 3.94 (3H).

Workup

  1. temperatureto warm to room temperature
  2. stirringstir for 1 hour
  3. customReaction mixture
  4. extractionextracted with EtOAc (2×150 mL)
  5. dry with materialThe combined organic phase was dried (Na2SO4)
  6. concentrationconcentrated under vacuum The residue
  7. customwas chromatographed (80 g Redi-Sep column)
  8. washeluting from 100% heptane to 20:80 EtOAc

Sources & evidence

ORD record
ord-97cd4a0915b242a390217a8a2561aed9
Source dataset
uspto-grants-2013_04
Patent number
US08415310B2

Reaction notes

Loading…