Yield:1093865-36-1 52%

Reaction Conditions:

Stage #1: 1-bromo-3-chlorobenzenewith n-butyllithium in tetrahydrofuran at -78; for 1.33333 h;
Stage #2: m-bromobenzoic aldehyde in tetrahydrofuran at -78; for 0.166667 h;
Stage #3: with ammonia hydrochloride in tetrahydrofuran;lithium hydroxide monohydrate at -78 - 20;

Steps:

19.1

A solution of l-bromo-3-chlorobenzene (20 g, 104 mmol) in anhydrous THF (125 mL) under N₂ was cooled to -78 ⁰C, ?-BuLi (2.5 M, 42 mL, 105 mmol) was then added drop wise over 20 min. After stirring an additional hour, 3- bromobenzaldehyde (12.5 mL, 104 mmol) was added drop wise and the reaction was stirred for another 10 min at -78 ⁰C. Sat. NH₄Cl (100 mL) was added and the reaction was warmed to room temperature and extracted with ether (300 mL). The ether layer was extracted with three 75 mL portions of 1 M sodium bisulfite, 75 mL of 1 M sodium hydroxide, 75 mL of water, and 75 mL of brine. The ether layer was dried over MgSO₄ and the solvent removed to give crude product, which was purified by chromatography on silica gel (16 g, 52%). ¹H NMR (CDCl₃) δ 2.27 (br, IH), 5.75 (s, IH), 7.14-7.54 (m, 8H).

References:

WO2008/156817,2008,A2 Location in patent:Page/Page column 123-124