5-(4-(Hydroxymethyl)phenyl)picolinaldehyde synthesis

Yield:1429099-29-5 75%

Reaction Conditions:

with tetrakis(triphenylphosphine) palladium⁽⁰⁾;sodium carbonate in ethanol;water;toluene at 100; for 2 h;Inert atmosphere;

Steps:

11.1 Step 1: 5-(4-(hydroxymethyl)phenyl)picolinaldehyde

Step 1: 5-(4-(hydroxymethyl)phenyl)picolinaldehyde Toluene/EtOH100 °C, 2hTo a solution of 5-bromopicolinaldehyde (0.7 g, 3.76 mmol) in toluene (8 mL) and EtOH (6 mL) was added (4-(hydroxymethyl)phenyl) boronic acid (0.68 g, 4.516 mmol), 2M Na₂C0₃ (5.6 mL, 11.3 mmol) and Pd(PPh₃)₄(0.2 mg, 0.188 mmol) under argon. The mixture was degassed and heated to 100°C and stirred for 2 h. After completion of the reaction by monitoring with TLC (60% EtOAchexane), the resulting mixture was filtered with Celite reagent and the filtrate was separated. The filtrate was concentrated, extracted with EtOAc (2x 100 mL), washed with water (100 mL), dried over a₂S0₄ and concentrated in vacuo. The resulting residue was purified by a Biotage Isolera One column purifier (silica gel 100-200?) using 38% ethyl acetate in hexane to provide a yellow solid (0.6 g, 75% yield). ^XH NMR (400 MHz, DMSO-d₆): ? 10.01 (s, IH), 9.14 (d, IH), 8.306 (dd, IH), 7.98 (d, IH), 7.80 (d, 2H), 7.47 (d, 2H), 5.25 (s, IH), 4.56 (d, 2H); LC-MS: m/z 214.3 [M+H]⁺.

References:

WO2013/49565,2013,A1 Location in patent:Page/Page column 49-50