Synthesis
Synthesis of ethyl 4-(4-fluorophenyl)-2,4-dioxobutanoate: In a 2L round-bottomed flask fitted with a reflux condenser tube and a CaCl2 drying tube, sodium metal (49.9 g, 2.17 mol, 3.0 eq.) was slowly dissolved in ethanol (1.0 L). After the resulting sodium ethanol solution was cooled to about 10°C, a mixture of 4-fluoroacetophenone (100.0 g, 0.72 mol) and diethyl oxalate (295 mL, 2.17 mol, 3.0 eq.) was slowly added. The reaction mixture was stirred for about 15 minutes and then placed in a refrigerator to stand overnight. Subsequently, the reaction mixture was poured into a mixture consisting of concentrated hydrochloric acid solution (300 mL) and ice (about 1 kg). The resulting precipitate was collected by filtration and washed with plenty of water and finally dried in a vacuum dryer using P2O5/KOH. The product was a light yellow powder, yield: 165.5 g (96% yield).
References
[1] Patent: WO2015/95337, 2015, A2. Location in patent: Paragraph 0030
[2] Synthetic Communications, 2013, vol. 43, # 1, p. 110 - 117
[3] Patent: WO2015/196071, A1. Location in patent: Paragraph 0520
[3] Patent: , 2015, . Location in patent: Paragraph 0520
[5] Patent: WO2017/40606, 2017, A1. Location in patent: Paragraph 0465
