2-Chloro-4-fluoro-1-(2-methoxyethoxy)benzene synthesis

Yield:1036383-28-4 98%

Reaction Conditions:

with potassium carbonate in acetonitrile at 80; for 12 h;

Steps:

A A. 2-Chloro-4-fluoro- 1 -(2-methoxyethoxy)benzene.

To a solution of 2-chloro-4- fluoro-phenol (5 g, 34.12 mmol) and 1-bromo-2-methoxy-ethane (5.69 g, 40.94 mmol, 3.85 mL) in MeCN (100 mL) was added K₂CO₃ (9.43 g, 68.24 mmol). The reaction mixture was stirred at 80 °C for 12 hrs. The reaction mixture was cooled and diluted with H₂O (50 mL), and then diluted with EtOAc (50 mL × 3). The combined organic layers were washed with brine (50 mL × 2), dried over anhydrousNa₂SO₄, filtered and concentrated under reduced pressure. Purification (FCC, SiO₂, Petroleum ether/Ethyl acetate=1/0 to 20/1) afforded the title compound (6.9 g, 98%) as yellow oil. ¹H NMR (400 MHz, CDCl₃) δ = 7.14 - 7.12 (m, 1H), 6.93 - 6.91 (m, 2H), 4.15 (t, J= 4.8 Hz, (0306) 2H), 3.78 (t, J= 4.8 Hz, 2H), 3.18 (s, 3H).

References:

WO2021/156787,2021,A1 Location in patent:Page/Page column 81