ethyl 5-bromo-2-(4-fluorophenyl)benzofuran-3-carboxylate synthesis

Yield:1333340-13-8 14.3%

Reaction Conditions:

with di-tert-butyl peroxide;iron(III) chloride hexahydrate in 1,2-dichloro-ethane; for 6 h;Inert atmosphere;Reflux;

Steps:

Synthesisof Compound 4

A mixture of compound 3 (130 g, 0.6 mol), 4-bromophenol (311 g, 1.8 mol) andFeCl₃·6H₂O (19.5 g, 0.09 mol) in DCE (700 mL) wasstirred at RT, and then 2-(tert-butylperoxy)-2-methylpropane (193g, 1.32 mol) was added drop wise under nitrogen. After heated to reflux and stirred 6 hours,the mixture was cooled to RT, quenched with saturated NaHSO₃, andextracted with DCM. The organic phaseswere washed with water, brine and dried over Na₂SO₄, filtered and evaporated.The residue was purified by column chromatography (PE : DCM = 15 : 1) to give thecrude product, which was crystallizedfrom cold MeOHto afford compound 4 (37 g, yield: 14.3%) as solid_. ¹H-NMR (CDCl₃, 400 MHz) d 8.12 (s, 1H), 7.97~8.01 (m, 2H), 7.37 (d, J = 4.0 Hz, 1H), 7.32 (d, J =8.0 Hz, 1H), 7.11 (t, J = 8.0 Hz,2H), 4.32~4.38 (m, 2H), 1.36 (t, J =8.0 Hz, 3H).

References:

He, Shuwen;Li, Peng;Dai, Xing;McComas, Casey C.;Du, Chunyan;Wang, Ping;Lai, Zhong;Liu, Hong;Yin, Jingjun;Bulger, Paul G.;Dang, Qun;Xiao, Dong;Zorn, Nicolas;Peng, Xuanjia;Nargund, Ravi P.;Palani, Anandan [Tetrahedron Letters,2014,vol. 55,# 14,p. 2212 - 2216] Location in patent:supporting information