Bromine → methyl-N-[3,5-dichloro-4-(2-bromo-4-methoxy-5-isopropylphenoxy)benzoyl]glycine

HRID 860957Notes

Reaction equation

HRID 860957 reaction equation
[Br:1]Br.[CH3:3][N:4]([C:9](=[O:30])[C:10]1[CH:15]=[C:14]([Cl:16])[C:13]([O:17][C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[C:20]([CH:26]([CH3:28])[CH3:27])[CH:19]=2)=[C:12]([Cl:29])[CH:11]=1)[CH2:5][C:6]([OH:8])=[O:7].C([O-])(=O)C.[Na+].S([O-])([O-])(=O)=S.[Na+].[Na+]>O.C(O)(=O)C>[CH3:3][N:4]([C:9](=[O:30])[C:10]1[CH:11]=[C:12]([Cl:29])[C:13]([O:17][C:18]2[CH:19]=[C:20]([CH:26]([CH3:28])[CH3:27])[C:21]([O:24][CH3:25])=[CH:22][C:23]=2[Br:1])=[C:14]([Cl:16])[CH:15]=1)[CH2:5][C:6]([OH:8])=[O:7]

Participants

7

Reactant 4

HCID 24408Bromine2×HCID 24477Sodium ThiosulfateHCID 517045Sodium Acetate2×HCID 69387388methyl-N-[3,5-dichloro-4-(4-methoxy-3-isopropylphenoxy)benzoyl]glycine

Product 1

HCID 69384859methyl-N-[3,5-dichloro-4-(2-bromo-4-methoxy-5-isopropylphenoxy)benzoyl]glycineYield 2%

Reagents, catalysts & solvents 2

HCID 962WaterCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
40 °C

Procedure

Bromine (13 μL, 0.26 mmol) was added dropwise to a well stirred mixture of methyl-N-[3,5-dichloro-4-(4-methoxy-3-isopropylphenoxy)benzoyl]glycine (50 mg, 0.12 mmol), acetic acid (1.0 mL), sodium acetate (35 mg, 0.26 mmol) and a few drops of water. The reaction mixture was stirred at room temperature for three hours, heated at 40° C. for 90 minutes and finally left at room temperature for 16 hours. Sodium acetate (17 mg) and bromine (6 μL) was added and the reaction mixture heated to 40° C. for two hours. The reaction mixture was left at 4° C. for three days. Sodium thiosulfate (saturated) was added and the yellow mixture concentrated. The residue was diluted with ethyl acetate and washed with water. The aqueous phase was extracted with dichloromethane, the combined organic phases washed with brine and dried over sodium sulfate. After concentration, the residue was purified on column (hplc, C8, acetonitrile/water/formic acid, gradient elution from 20/80/0.5 to 100/0/0) to give 1.0 mg (2%) of methyl-N-[3,5-dichloro-4-(2-bromo-4-methoxy-5-isopropylphenoxy)benzoyl]glycine.

Workup

  1. stirringThe reaction mixture was stirred at room temperature for three hours
  2. temperaturethe reaction mixture heated to 40° C. for two hours
  3. waitThe reaction mixture was left at 4° C. for three days
  4. concentrationthe yellow mixture concentrated
  5. additionThe residue was diluted with ethyl acetate
  6. washwashed with water
  7. extractionThe aqueous phase was extracted with dichloromethane
  8. washthe combined organic phases washed with brine
  9. dry with materialdried over sodium sulfate
  10. concentrationAfter concentration
  11. customthe residue was purified on column (hplc, C8, acetonitrile/water/formic acid, gradient elution from 20/80/0.5 to 100/0/0)

Sources & evidence

ORD record
ord-efd972e560a44770af8f011f308f3567
Source dataset
uspto-grants-2006_12
Patent number
US07153997B2

Reaction notes

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