Tetrahydrofuran → 2-(4,6-Dichloropyridin-2-yl)-5-methylthiazole

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A dry 25 mL schlenk flask equipped with a stir bar and placed under N2 atmosphere was charged with THF (7 mL) and 2-bromo-5-methylthiazole (610 mg, 3.43 mmol). The solution was cooled to −78° C. To the solution was added n-butyllithium in hexanes (1.37 mL, 3.43 mmol) upon which the solution immediately turned dark/golden. The solution was stirred for 5 minutes. To the solution was added zinc(II) chloride in THF (6.85 mL, 3.43 mmol) upon which the solution lightened to a golden color. The solution was immediately warmed to r.t. with a water bath, with stirring for 30 minutes. To the reaction solution was added 2,4,6-trichloropyridine (250 mg, 1.37 mmol) and Pd(dppf)Cl2 (100 mg, 0.137 mmol). The flask was sealed and then was placed in a 60° C. oil bath with stirring for 16 h. The reaction solution was transfered to a 500 mL reparatory funnel and was diluted with EtOAc (100 mL), then washed with brine (50 mL). The organic phase was dried over MgSO4; filtered; then concentrated in vacuo to afford a dark amber solid. This material was subjected to silica gel chromatography to afford 2-(4,6-dichloropyridin-2-yl)-5-methylthiazole as a white solid (33 mg, 8%): 1H-NMR (500 MHz, CDCl3) δ 8.07 (d, J=1.7 Hz, 1H), 7.59 (d, J=1.1 Hz, 1H), 7.32 (d, J=1.6 Hz, 1H), 2.55 (d, J=1.1 Hz, 3H); and 2,2′-(4-chloropyridine-2,6-diyl)bis(5-methylthiazole) as a white solid (160 mg, 48%): 1H-NMR (500 MHz, CDCl3) 8.10 (s, 2H), 7.60 (d, J=1.3 Hz, 2H), 2.59-2.55 (m, 6H).

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