Synthesis
General procedure for the synthesis of tert-butyl 4-fluorobenzoate from 4-fluorobenzoic acid and di-tert-butyl dicarbonate: to a solution of 4-fluorobenzoic acid (10 g, 0.07 mol) in tert-butanol (200 ml) was added 4-dimethylaminopyridine (4.36 g, 35.7 mmol) followed by the slow addition of di-tert-butyl dicarbonate (31.1 g, 0.14 mol) at 0 °C. The reaction mixture was stirred at room temperature for 4 hours. After completion of the reaction, it was diluted by adding water (200 ml) and extracted with dichloromethane. The organic phases were combined and the solvent was removed by evaporation under reduced pressure. The crude product was purified by column chromatography (silica gel as stationary phase and petroleum ether/ethyl acetate = 20:1 as eluent) to afford tert-butyl 4-fluorobenzoate (10.2 g, 74% yield). The product was characterized by 1H-NMR (300 MHz, CD3OD): δ 7.98 (m, 2H), 7.15 (m, 2H), 1.59 (s, 9H).
References
[1] Patent: WO2013/75083, 2013, A1. Location in patent: Paragraph 00564; 00565
[2] Patent: US9206128, 2015, B2. Location in patent: Page/Page column 252; 253
