Sodium Carbonate → 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) and Na2CO3 (2M, 100 mL, 19.39 g). The reaction mixture was purged with argon for 45 min, Pd(PPh3)4 (3.5 g, 3.04 mmol) added, and the 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 layers were washed with ice-cold water (2×100 mL), followed by brine solution (50 mL). The organic layer was dried over sodium sulfate, filtered and concentrated under reduced pressure to obtain 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-d6): δ 7.98 (dd, 2H), 7.88 (d, 1H); 7.91 (d, 1H), 7.88 (d, 1H), 7.31 (t, 2H); LC-MS m/z calculated for [M+H]+ 180.02 found 179.91.

1. customThe reaction mixture was purged with argon for 45 min
2. temperatureThe reaction mixture was cooled to room temperature
3. customquenched with saturated sodium bicarbonate solution (2×100 mL)
4. extractionextracted with ethyl acetate (2×100 mL)
5. washThe combined organic layers were washed with ice-cold water (2×100 mL)
6. dry with materialThe organic layer was dried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customto obtain crude product
10. customThe crude product was purified by column chromatography (100-200 mesh silica gel; using 10% ethyl acetate in hexane)

ORD record

ord-76a706c7e0344116bbfe790707454d9c

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809372B2