5-Borono-4-chloro-2-methoxybenzoic acid synthesis

Yield:-

Reaction Conditions:

with potassium phosphate;tris-(dibenzylideneacetone)dipalladium⁽⁰⁾;tri tert-butylphosphoniumtetrafluoroborate in tetrahydrofuran;water at 20; for 3 h;Product distribution / selectivity;

Steps:

38.C

N₂ was bubbled through a solution of THF (8 ml.) and water (2 mL) containing δ-carboxy^-chloro^-methoxy-phenylboronic acid (460.8 mg, 2 .0 mmol) and δ-bromo^-trifluoromethyl-isonicotinonitrile 1-1 (478 mg, 1.9 mmol) for 10 minutes. K₃PO₄ (1.2 g, 5.7 mmol), t-Bu₃P.HBF₄ (82.7 mg, 0.28 mmol), and Pd₂dba₃ (91.0 mg, 0.1 mmol) were added under N₂ atmosphere. The mixture was sealed, stirred at rt for 3 hrs, and diluted with ethyl acetate. The organic layer was separated, washed with brine, dried over MgSO₄, filtered and concentrated. The residue was purified via silica gel flash column chromatography eluting with 10% MeOH in dichloromethane to give 4-chloro-5-(4-cyano-6-trifluoromethyl-pyridin-3-yl)-2-methoxy-benzoic acid (301 mg).

References:

WO2008/124610,2008,A1 Location in patent:Page/Page column 120