6-cyanobenzo[b]thiophen-2-ylboronic acid synthesis

Yield:1119899-35-2 72%

Reaction Conditions:

Stage #1: benzo[b]thiophene-6-carbonitrilewith n-butyllithium in tetrahydrofuran;hexanes at -90; for 0.5 h;
Stage #2: with Trimethyl borate in tetrahydrofuran;hexanes at -90; for 0.5 h;
Stage #3: with hydrogenchloride;water in tetrahydrofuran;hexanes at -90 - 30; for 0.5 h;

Steps:

35

[0167] Compound 23 (14 g, 0.088 mol) in dry THF (350 mL) was purged with nitrogen. The mixture was then cooled (-90 ⁰C) with liquid nitrogen bath and ra-BuLi (2.5 M in hexanes, 42 niL, 0.105 mol) was added dropwise with stirred. The mixture was stirred for a further 30 min, and B(OMe)₃ (18 g, 0.173 mol) was added at -90 ⁰C. After 30 min, aqueous HCl (2M, 200 mL) was added. The mixture was stirred for a further 30 min, allowed to warm to room temperature (30 ⁰C), poured into water (100 mL). The mixture was extracted with EtOAc (400 mLx3). The combined organic layers were washed with water, brine, dried over Na₂SO₄ and concentrated to give a crude product, which was crystallized with EtOAc/PE (1:2, 100 mL) to give the title compound (12 g, 72%) as a white solid.

References:

WO2009/26345,2009,A1 Location in patent:Page/Page column 43-44