Triethylamine → 2-Bromo-5-fluoro-N-methoxy-N-methylbenzamide

HRID 632658Notes

Reaction equation

HRID 632658 reaction equation
[Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4](O)=[O:5].Cl.[CH3:13][NH:14][O:15][CH3:16].OC1C2N=NNC=2C=CC=1.C(N(CC)CC)C>C(Cl)Cl>[Br:1][C:2]1[CH:10]=[CH:9][C:8]([F:11])=[CH:7][C:3]=1[C:4]([N:14]([O:15][CH3:16])[CH3:13])=[O:5]

Participants

6

Reactant 4

HCID 8471TriethylamineHCID 81138Methanamine, N-methoxy-, hydrochloride (1:1)HCID 27781812-Bromo-5-fluorobenzoic acidHCID 178418300HCID 178418300, compound

Product 1

HCID 227354792-Bromo-5-fluoro-N-methoxy-N-methylbenzamide

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-bromo-5-fluorobenzoic acid (2.0 g, 9.13 mmol) in DCM (90 mL) at room temperature was added N,O-dimethylhydroxylamine hydrochloride (1.069 g, 10.96 mmol), N-(3-dimethylaminopropyl)-K-ethylcarbodiimide hydrochloride (2.276 g, 11.87 mmol), hydroxybenzotriazole (1.818 g, 11.87 mmol) and triethylamine (2.55 mL, 18.26 mmol). The resulting mixture was stirred at room temperature for 5.5 h after which time the reaction was quenched by addition of sat. aq. NaHCO3 solution and the layers separated. The organic layer was then washed with brine, dried over anhydrous MgSO4, filtered and concentrated in vacuo. The resulting crude material was purified by column chromatography (SiO2, 0-40% EtOAc/Hexanes) to afford 2-bromo-5-fluoro-N-methoxy-N-methylbenzamide as a white solid. 1H NMR (400 MHz, CDCl3) δ ppm 7.54 (dd, J=8.8, 4.9 Hz, 1H), 7.05 (dd, J=8.2, 3.0 Hz, 1H), 7.00 (td, J=8.4, 3.0 Hz, 1H), 3.50 (s, 2H), 3.38 (s, 3H).

Workup

  1. customwas quenched by addition of sat. aq. NaHCO3 solution
  2. customthe layers separated
  3. washThe organic layer was then washed with brine
  4. dry with materialdried over anhydrous MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customThe resulting crude material was purified by column chromatography (SiO2, 0-40% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-2048b9ebf4d64ab4be72b682ef56c8ea
Source dataset
uspto-grants-2016_04
Patent number
US09321746B2

Reaction notes

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