Potassium Carbonate → 4-Bromo-3-fluoro-N-methoxy-N-methylbenzamide

HRID 2245951Notes

Reaction equation

HRID 2245951 reaction equation
C(Cl)(=O)C(Cl)=O.[Br:7][C:8]1[CH:16]=[CH:15][C:11]([C:12](O)=[O:13])=[CH:10][C:9]=1[F:17].Cl.[CH3:19][NH:20][O:21][CH3:22].C(=O)([O-])[O-].[K+].[K+]>C(Cl)Cl.O.CN(C=O)C>[Br:7][C:8]1[CH:16]=[CH:15][C:11]([C:12]([N:20]([O:21][CH3:22])[CH3:19])=[O:13])=[CH:10][C:9]=1[F:17]

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 65578Oxalyl chlorideHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27733414-Bromo-3-fluorobenzoic acid

Product 1

HCID 223138234-Bromo-3-fluoro-N-methoxy-N-methylbenzamideYield 99.2%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent2×

Procedure

Oxalyl chloride (38.1 mL, 0.450 mol) was slowly added to a mixture of 4-bromo-3-fluorobenzoic acid (49.3 g, 0.225 mol) in methylene chloride (300 mL), then DMF (1.0 mL) was added and the reaction was stirred at RT for 2 h. The volatiles were removed under reduced pressure and co-evaporated with toluene for 3 times. The residue was then dissolved in methylene chloride (100 mL). The solution was added dropwise to a mixture of N,O-dimethyl-hydroxylamine hydrochloride (30.7 g, 0.315 mol) and potassium carbonate (120 g, 0.90 mol) in methylene chloride (300 mL) and water (300 mL). The reaction was stirred at RT for 2 h. The organic layer was separated. The aqueous layer was extracted with methylene chloride (2×50 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure to give the product (58.5 g, 99%). Analytical LCMS: (M+H)+=261.9/263.9.

Workup

  1. customThe volatiles were removed under reduced pressure and co-evaporated with toluene for 3 times
  2. dissolutionThe residue was then dissolved in methylene chloride (100 mL)
  3. stirringThe reaction was stirred at RT for 2 h
  4. customThe organic layer was separated
  5. extractionThe aqueous layer was extracted with methylene chloride (2×50 mL)
  6. washThe combined organic layers were washed with brine
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-73c43dc6e6ad46b981a267b1293ab748
Source dataset
uspto-grants-2010_03
Patent number
US07683060B2

Reaction notes

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