2-Bromothiazole → 2-(4-Fluorophenyl)thiazole

Temperature

95 °C

To a stirred solution of (4-fluorophenyl)boronic acid (10 g, 60.9 mmol) in toluene (70 mL) and ethanol (200 mL) was added 2-bromothiazole (12.7 g, 91.4 mmol), followed by Pd(PPh3)4 (3.5 g, 3.04 mmol). The reaction mixture was purged with argon for 20 min, Na2CO3 solution (2M, 100 mL, 19.39 g) added, and the reaction mixture stirred at 95° C. for 5 h. The reaction mixture was cooled to room temperature, quenched with saturated sodium bicarbonate solution (2×100 mL), and extracted with ethyl acetate (2×100 mL). The combined organic layer was washed with ice-cold water (2×100 mL) followed by brine solution, dried over sodium sulfate, filtered and concentrated under reduced pressure to obtained crude product. The crude product was purified by column chromatography (100-200 mesh silica gel) using 10% ethyl acetate in hexane to obtain 2-(4-fluorophenyl)thiazole as white solid (9.0 g, 82% yield). 1H NMR (400 MHz, DMSO): 7.98 (dd, 2H, J=6.8 & 14.0 Hz), 7.88 (d, 1H, J=4.8 Hz), 7.91 (d, 1H, J=2.8 Hz), 7.88 (d, 1H, J=4.8 Hz), 7.31 (t, 2H, J=8.8 & 17.2 Hz).

1. customThe reaction mixture was purged with argon for 20 min
2. additionNa2CO3 solution (2M, 100 mL, 19.39 g) added
3. temperatureThe reaction mixture was cooled to room temperature
4. customquenched with saturated sodium bicarbonate solution (2×100 mL)
5. extractionextracted with ethyl acetate (2×100 mL)
6. washThe combined organic layer was washed with ice-cold water (2×100 mL)
7. dry with materialdried over sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customto obtained crude product
11. customThe crude product was purified by column chromatography (100-200 mesh silica gel)

ORD record

ord-382d11f1061e4e3f9ff6041c0ac39581

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809372B2