Hydrochloric Acid → N-(4-Bromo-2-fluoro-6-methylphenyl)pivalamide

HRID 1372531Notes

Reaction equation

HRID 1372531 reaction equation
[C:1](Cl)(=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3].[Br:8][C:9]1[CH:15]=[C:14]([CH3:16])[C:12]([NH2:13])=[C:11]([F:17])[CH:10]=1.O.Cl>N1C=CC=CC=1>[Br:8][C:9]1[CH:15]=[C:14]([CH3:16])[C:12]([NH:13][C:1](=[O:6])[C:2]([CH3:5])([CH3:4])[CH3:3])=[C:11]([F:17])[CH:10]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 962WaterHCID 62493Pivaloyl chlorideHCID 179726714-Bromo-2-fluoro-6-methylaniline

Product 1

HCID 17972716N-(4-Bromo-2-fluoro-6-methylphenyl)pivalamideYield 49%

Reagents, catalysts & solvents 1

HCID 1049PyridineSolvent

Procedure

Pivaloyl chloride (4 mL, 38.4 mmol) was added slowly (caution—exothermic reaction) to an ice cold solution of the crude 4-bromo-2-fluoro-6-methylaniline from step 4 (about 32 mmol) in pyridine (20 mL). After the addition, the ice bath was removed and the warm reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was poured into a water solution of 1 N HCl and extracted with EtOAc. The organic layer was washed with 1N HCl three times, dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by flash chromatography on a Biotage 40M KP-Sil column, eluting with 9:1 hexanes-EtOAc. The product containing fractions were evaporated under vacuum to provide N-(4-bromo-2-fluoro-6-methylphenyl)-2,2-dimethylpropanamide (4.3 g, 49% for 3 steps) as a yellow solid.

Workup

  1. additionAfter the addition
  2. customthe ice bath was removed
  3. customthe warm reaction mixture
  4. extractionextracted with EtOAc
  5. washThe organic layer was washed with 1N HCl three times
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe residue was purified by flash chromatography on a Biotage 40M KP-Sil column
  10. washeluting with 9:1 hexanes-EtOAc
  11. additionThe product containing fractions
  12. customwere evaporated under vacuum

Sources & evidence

ORD record
ord-54267338b9f14b989715c414d2f7f447
Source dataset
uspto-grants-2007_01
Patent number
US07157604B2

Reaction notes

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