1-bromo-3-(2-methoxyethylsulfanyl)benzene synthesis

Yield:1021169-59-4 81%

Reaction Conditions:

Stage #1: 3-Bromothiophenolwith sodium hydride in N,N-dimethyl-formamide at 20; for 0.5 h;
Stage #2: 2-Bromoethyl methyl ether in N,N-dimethyl-formamide; for 17 h;

Steps:

1.17.A

Step A: Preparation of Intermediate (3-Bromophenyl)(2-methoxyethyl)sulfane.To a suspension of sodium hydride (96.6 mg, 2.42 mmol) in DMF (4.2 mL) was added 3-bromobenzenethiol (0.22 mL, 2.132 mmol). After stirring at room temperature for 30 min, 1- bromo-2-methoxyethane (0.22 mL, 2.341 mmol) was added to the reaction mixture. After stirring for 17 h, the reaction mixture was quenched with H₂O and extracted with EtOAc. The combined organic layers were washed with H₂O, brine, dried over MgSO₄ and concentrated. The residue was purified through a silica gel column with 15% EtOAc/ 85% hexanes to afford the title compound (425.1 mg, 81%) as a colorless oil. ¹H NMR (400 MHz, Methanol-^) δ ppm 3.13 (t, J= 6.5 Hz, 2 H), 3.33 (s, 3 H), 3.57 (t, J = 6.5 Hz, 2 H), 7.20 (dd, J= 7.9, 7.9 Hz, 1 H), 7.30 - 7.35 (m, 2 H), 7.50 - 7.52 (m, 1 H).

References:

WO2008/48609,2008,A1 Location in patent:Page/Page column 64