p-Toluenesulfonic acid → Methyl 3-bromo-2-fluorobenzoate

HRID 1264519Notes

Reaction equation

HRID 1264519 reaction equation
[Br:1][C:2]1[C:3]([F:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([OH:7])=[O:6].[CH3:12]OC(OC)OC.C1(C)C=CC(S(O)(=O)=O)=CC=1>CO>[Br:1][C:2]1[C:3]([F:11])=[C:4]([CH:8]=[CH:9][CH:10]=1)[C:5]([O:7][CH3:12])=[O:6]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 9005Trimethyl orthoformateHCID 27363133-Bromo-2-fluorobenzoic acid

Product 1

HCID 21584505Methyl 3-bromo-2-fluorobenzoateYield 84%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of 3-bromo-2-fluorobenzoic acid. (0.219 g, 1 mmol) in dry methanol (5 ml) under nitrogen was treated with trimethylorthoformate (0.22 ml, 2 mmol) and p-toluenesulfonic acid (catalytic amount), and then heated under reflux. After 16 h, the mixture was evaporated and the residue partitioned between water and Et2O. The organic layer was washed with sat. sodium hydrogen carbonate solution, water, brine, dried (MgSO4) and evaporated to give methyl 3-bromo-2-fluorobenzoate (0.195 g, 0.84 mmol, 84%): 1H NMR (CDCl3) δ 7.90-7.85 (m, 1H), 7.71-7.65 (m, 1H), 7.10 (dt, 1H, J=8.0, 1.0 Hz) and 3.94 (s, 3H): MS (EI) 232 (M+).

Workup

  1. temperatureheated
  2. temperatureunder reflux
  3. customthe mixture was evaporated
  4. customthe residue partitioned between water and Et2O
  5. washThe organic layer was washed with sat. sodium hydrogen carbonate solution, water, brine
  6. dry with materialdried (MgSO4)
  7. customevaporated

Sources & evidence

ORD record
ord-0ec6fe9450f64b1ab7bfbbd45dd56b74
Source dataset
uspto-grants-2003_04
Patent number
US06544970B2

Reaction notes

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