Phosphorus oxychloride → 2177297-18-4

HRID 2264372Notes

Reaction equation

HRID 2264372 reaction equation
P(Cl)(Cl)(Cl)=O.[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([NH2:14])=[C:9]([F:15])[CH:8]=1.[CH:16]([NH:19][C:20](=O)[CH3:21])([CH3:18])[CH3:17]>C1(C)C=CC=CC=1>[Br:6][C:7]1[CH:12]=[C:11]([F:13])[C:10]([NH:14][C:20](=[N:19][CH:16]([CH3:18])[CH3:17])[CH3:21])=[C:9]([F:15])[CH:8]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 136874N-(1-Methylethyl)ethanamideHCID 6101914-Bromo-2,6-difluoroaniline

Product 1

HCID 674267372177297-18-4Yield 84.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
15 °C

Procedure

Add phosphoryl chloride (16.0 kg) to a mixture of 4-bromo-2,6-difluoro-phenylamine (14.5 kg), N-isopropyl acetamide (8.5 kg), TEA (10.6 kg) in toluene (115 kg) at <20° C. Stir at 10-20° C. until complete by HPLC. Remove the solvent under vacuum and add MtBE (64 kg). Adjust the pH of the mixture with 10% aq. sodium carbonate (250 kg). Filter the mixture and rinse the cake with MtBE (11×2 kg). Separate the phases and wash the aqueous layer with MtBE (22×2 kg). Combine the organic layers and concentrate, filter and wash with cyclohexane (0.6 kg) and dry to afford 17.2 kg of the title compound. MS (ES+): m/z=292 (M+H)+.

Workup

  1. customRemove the solvent under vacuum
  2. additionadd MtBE (64 kg)
  3. filtrationFilter the mixture
  4. washrinse the cake with MtBE (11×2 kg)
  5. customSeparate the phases
  6. washwash the aqueous layer with MtBE (22×2 kg)
  7. concentrationCombine the organic layers and concentrate
  8. filtrationfilter
  9. washwash with cyclohexane (0.6 kg)
  10. customdry

Sources & evidence

ORD record
ord-fcbb7e39e76b470f81bf8793099295ec
Source dataset
uspto-grants-2010_12
Patent number
US07855211B2

Reaction notes

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