Reaction #7105

Reaction equation

3-bromo-2-fluorobenzoic acid

trimethylorthoformate

p-toluenesulfonic acid

→

methyl 3-bromo-2-fluorobenzoate

Yield 84.0%

Solvents

methanol

Conditions

Workup

1. 1
   Temperatureheated
2. 2
   Temperatureunder reflux
3. 3
   Otherthe mixture was evaporated
4. 4
   Otherthe residue partitioned between water and Et2O
5. 5
   WashThe organic layer was washed with sat. sodium hydrogen carbonate solution, water, brine
6. 6
   Dryingdried (MgSO4)
7. 7
   Otherevaporated

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+).

Source