Pyridine → 2-Bromo-6-(2-chloroacetamido)benzoic acid

HRID 400536Notes

Reaction equation

HRID 400536 reaction equation
[NH2:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([Br:11])[C:3]=1[C:4]([OH:6])=[O:5].N1C=CC=CC=1.[Cl:18][CH2:19][C:20](Cl)=[O:21]>C1(C)C=CC=CC=1>[Br:11][C:7]1[CH:8]=[CH:9][CH:10]=[C:2]([NH:1][C:20](=[O:21])[CH2:19][Cl:18])[C:3]=1[C:4]([OH:6])=[O:5]

Participants

5

Reactant 3

HCID 1049PyridineHCID 6577Chloroacetyl chlorideHCID 105606492-Amino-6-bromobenzoic acid

Product 1

HCID 545087422-Bromo-6-(2-chloroacetamido)benzoic acidYield 34.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

To a stirred solution of 2-amino-6-bromo-benzoic acid (6) (3.06 g, 14.2 mmol) in toluene (75 mL) cooled to 0° C. in an ice-bath was added pyridine (0.60 mL, 7.10 mmol) followed by a solution of chloroacetyl chloride (2.26 mL, 28.4 mmol) in toluene (75 mL) drop-wise over 1 hr. The reaction mixture was allowed to warm to RT, and was heated at 115° C. for 3 hr and then allowed to cool to RT. The solvent volume was reduced by half by evaporation in vacuo. Upon standing overnight, the product precipitated and was collected by filtration to afford 2-bromo-6-(2-chloroacetamido)benzoic acid (7a) (1.44 g) as a white solid: m/z 290/292 (M+H)+ (ES+). The filtrate was concentrated in vacuo and the residue triturated with ethanol/heptane to afford 2-bromo-6-(2-hydroxyacetamido)benzoic acid (7b) (1.02 g, combined yield, 59%): m/z 274/276 (M+H)+ (ES+). Both 7a and 7b can be used without further purification in the next step.

Workup

  1. temperaturewas heated at 115° C. for 3 hr
  2. temperatureto cool to RT
  3. customThe solvent volume was reduced by half by evaporation in vacuo
  4. customthe product precipitated
  5. filtrationwas collected by filtration

Sources & evidence

ORD record
ord-fef50a5a7f114cf5a7835d6a01b9cbc8
Source dataset
uspto-grants-2014_06
Patent number
US08741909B2

Reaction notes

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