methyl 4-bromo-2-fluorobenzoate

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-bromo-2-fluorobenzoic acid (30 g, 0.14 mol) of was dissolved in methanol with a few drops of sulfuric acid. The reaction medium was refluxed for 20 hours. The cooled reaction mixture was evaporated and the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution. The organic layer was separated and washed with brine, dried over sodium sulfate, filtered and evaporated to give methyl 4-bromo-2-fluorobenzoate (20.7 g, yield 64%) as a white solid. 1H-NMR (400 MHz, DMSO-d6) δ (ppm); 3.85 (s, 3H), 7.55-7.58 (m, 1H), 7.70-7.73 (m, 1H), 7.79-7.83 (m, 1H); LC-MS (ESI) m/z: 233 (M+1)+, 235 (M+3)+ The reaction medium was refluxed for 20 hours The cooled reaction mixture was evaporated the residue partitioned between ethyl acetate and saturated aqueous sodium bicarbonate solution The organic layer was separated washed with brine dried over sodium sulfate filtered evaporated

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-(Tributylstannyl)pyridine (11.2 g, 30.4 mmol) was dissolved in toluene (240 mL), methyl 4-bromo-2-fluorobenzoate (7.4 g, 33.4 mmol) and tetrakis(triphenyl-phosphine) Pd (1.75 g) were added thereto. The mixture was poured into water, extraction was carried out with ethyl acetate, the organic phase was dried and the solvent was evaporated. The residue was purified by column chromatography (silica gel, petroleum ether:ethyl acetate 50:1 to 10:1) to give methyl 2-fluoro-4-(pyridin-2-yl)benzoate (2.5 g, yield 35%). 1H-NMR (400 MHz, CDCl3) δ (ppm): 3.93 (s, 3H), 7.31-7.34 (m, 1H), 7.76-7.85 (m, 4H), 8.05 (t, J=7.6 Hz, 1H), 8.72-8.74 (m, 1H); LC-MS (ESI) m/z: 232 (M+1)+. the organic phase was dried the solvent was evaporated The residue was purified by column chromatography (silica gel, petroleum ether:ethyl acetate 50:1 to 10:1)