Dimethyl Sulfoxide → 5-(4-Fluoro-6-methylpyridin-2-yl)thiazole

Reaktionsgleichung

Cl[C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[S:13][CH:12]=[N:11][CH:10]=2)[CH:3]=1.[F-:14].[Cs+].CS(C)=O>CCOC(C)=O>[F:14][C:2]1[CH:7]=[C:6]([CH3:8])[N:5]=[C:4]([C:9]2[S:13][CH:12]=[N:11][CH:10]=2)[CH:3]=1

Komponenten

Versuchsvorschrift

To a 2 dram vial equipped with a stir bar and charged with the entirety of 5-(4-chloro-6-methylpyridin-2-yl)thiazole from step 1 was added CsF (200 mg, 1.32 mmol) and DMSO (0.7 mL). The vial was capped and then placed in a 140° C. heating block with stirring for 16 h. The reaction mixture was transfered to a 125 mL separatory funnel and was diluted with EtOAc (50 mL). The solution was twice washed with brine:water (25 mL:25 mL); dried over MgSO4; filtered; then concentrated in vacuo to afford an amber solid residue. This material was subjected to silica gel chromatography (hexanes:EtOAc) to afford 5-(4-fluoro-6-methylpyridin-2-yl)thiazole as a colorless solid (7.1 mg, 21% over two steps). 1H-NMR (500 MHz, CDCl3) 8.84 (d, J=0.3 Hz, 1H), 8.32 (d, J=0.3 Hz, 1H), 7.22 (dd, J=9.3, 1.7 Hz, 1H), 6.82 (dd, J=9.2, 2.0 Hz, 1H), 2.59 (s, 3H); MS: MS m/z 195.2 (M++1).