Sodium Carbonate → 5-Bromo-4-(4-chlorobenzyl)-2-(pyridin-4-yl)thiazole

Participants

Reaction Conditions

Reaction Steps

To a solution of 2,5-dibromo-4-(4-chlorobenzyl)thiazole (12.9 grams, 35.1 mmol) in DME (365 mL) was added pyridine-4-boronic acid (5.61 g, 45.6 mmol), 1M sodium carbonate (70.2 mL, 70.2 mmol), and PdCl2(dppf) (2.89 g, 3.51 mmol). The reaction was degassed with argon and stirred at 85° C. overnight. The reaction was cooled and taken up in ethyl acetate (400 mL) and saturated sodium bicarbonate (200 mL). The insolubles were filtered through celite and the bed was washed with ethyl acetate (100 mL). The layers were separated and the aqueous layer was extracted with ethyl acetate (100 mL). The combined organic layers were dried over MgSO4, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (ethyl acetate/DCM=0/100→70/30) followed by another silica gel chromatography (ethyl acetate/hexanes=0/100→100/0) to give 3.3 grams of the title compound as a brown solid (26% yield). LC/MS (FA) ES+ 365, 367. 1H NMR (300 MHz, CDCl3) δ: 8.70-8.67 (m, 2H), 7.70-7.67 (m, 2H), 7.28-7.26 (m, 4H), 4.13 (s, 2H).

Provenance & Evidence