Triethylamine → 3-bromo-2-fluoro-N-methoxy-N-methylbenzamide

HRID 1668734Notes

Reaction equation

HRID 1668734 reaction equation
C(N1C=CN=C1)(N1C=CN=C1)=O.[Br:13][C:14]1[C:15]([F:23])=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17](O)=[O:18].C(N(CC)CC)C.Cl.[CH3:32][NH:33][O:34][CH3:35]>ClCCl>[Br:13][C:14]1[C:15]([F:23])=[C:16]([CH:20]=[CH:21][CH:22]=1)[C:17]([N:33]([O:34][CH3:35])[CH3:32])=[O:18]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 682631,1'-CarbonyldiimidazoleHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27363133-Bromo-2-fluorobenzoic acid

Product 1

HCID 578252533-bromo-2-fluoro-N-methoxy-N-methylbenzamideYield 95.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Carbonyldiimidazole (7.76 g) was added portionwise to commercially available 3-bromo-2-fluorobenzoic acid [161957-56-8] (9.53 g) in dichloromethane (100 mL) over 30 min. The mixture was then heated at reflux for 30 min (until gas evolution ceased). The reaction was then cooled to room temperature and triethylamine (6.37 mL) followed by N,O-dimethylhydroxylamine hydrochloride (4.7 g) were added. The reaction was left to stir at room temperature for 16 h before being washed with 10% citric acid (2×100 mL) and sat. NaHCO3 (2×100 mL), and then dried over sodium sulfate. The solvent was removed by evaporation to yield the product as a brown oil (10.89 g, 95%). NMR (CDCl3): 3.20-3.80 (6H, m, ArCONCH3OCH3), 7.10 (1H, t, Ar), 7.35 (1H, td, Ar), 7.60 (1H, dt, Ar).

Workup

  1. temperatureThe mixture was then heated
  2. temperatureat reflux for 30 min (until gas evolution ceased)
  3. additionwere added
  4. waitThe reaction was left
  5. washbefore being washed with 10% citric acid (2×100 mL) and sat. NaHCO3 (2×100 mL)
  6. dry with materialdried over sodium sulfate
  7. customThe solvent was removed by evaporation

Sources & evidence

ORD record
ord-f9530baa446c4ef994a0c4b3172a91a9
Source dataset
uspto-grants-2011_08
Patent number
US07989449B2

Reaction notes

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