Pyridine → tert-Butyl 2-bromo-4-fluorobenzoate

Participants

Reaction Steps

To a suspension of 2-bromo-4-fluoro-benzoic acid (28.5 g, 0.13 mol) in dichloromethane (500 mL) at room temperature was added oxalyl chloride (11.35 mL, 0.26 mmol) followed by DMF (0.05 mL, catalytic, CARE vigorous gas evolution) and the reaction mixture stirred for 3 hours. The reaction mixture was concentrated in vacuo and the residue dissolved in DCM (500 mL) before treatment with a solution of tert-butanol (28.5 g, 0.26 mol) and pyridine (20.5 g, 0.26 mol). The resultant mixture was stirred at room temperature for 3 days before it was diluted with DCM and washed (1M aqueous sodium hydroxide, water, 0.1M aqueous HCl, water) dried (Na2SO4) filtered and concentrated in vacuo to give a yellow oil. The crude oil was subjected to flash chromatography (Si—PPC, gradient 0 to 20% ethyl acetate in cyclohexane) to give the title compound as a colourless oil (15.2 g, 42%). 1H NMR (CDCl3, 400 MHz) 7.76-7.73 (1H, m), 7.37 (1H, dd, J=8.36, 2.53 Hz), 7.05 (1H, ddd, J=8.70, 7.73, 2.53 Hz), 1.60 (9 H, s).

Provenance & Evidence