Yield:1183702-65-9 67%

Reaction Conditions:

with tetrakis(triphenylphosphine) palladium⁽⁰⁾;sodium carbonate in ethanol;water;N,N-dimethyl-formamide at 100;Inert atmosphere;

Steps:

12 2-Chloro-5-(3-fluorophenyl)benzoic acid (intermediate 111(g))

A solution of 3-fiuorophenyl boronic acid (500 mg, 3.5 mmol, 1.2 eq), 5-bromo-2- chlorobenzoic acid (700 mg, 3.0 mmol, 1.0 eq), Pd(PPh₃)4 (687 mg, 0.60 mmol, 0.2 eq) and Na₂C0₃ (2.52 g, 24 mmol, 8.0 eq) in a mixture of ethanol (5 mL), H₂0 (5mL) and DMF (20 mL) was stirred at 100°C under N₂ overnight. The reaction was quenched by addition of diluted HCl (to pH 3) and the aqueous phase was extracted with EtOAc. The combined organic extracts were washed with brine, dried (Na₂S04) filtered and evaporated in vacuo. The residue was purified by chromatography (petroleum ethenEtOAc 20:1 to 1 : 1) to give the title compound as a white solid (500 mg, 67 %). LC-MS : m/z 249.0, 251.0 [M-HV1H NMR (400 MHz, DMSO-d₆) ? 13.58 (br s, 1H), 8.06 (d, J= 2.2 Hz, 1H), 7.88 (dd, J = 8.3, 2.4 Hz, 1H), 7.65 (d, J= 8.4 Hz, 1H), 7.63 - 7.50 (m, 3H), 7.26 (br t, J= 8.2 Hz, 1H)

References:

WO2013/37705,2013,A2 Location in patent:Page/Page column 91