Nitrogen → 2-Fluoro-5-(thiazol-2-yl)benzonitrile

Temperature

85 °C

A solution of 2-bromothiazole (25 g, 153.4 mmol), (3-cyano-4-fluorophenyl)boronic acid (25.3 g, 153.3 mmol), K2CO3 (63.6 g, 460 mmol) and 3:1 DME/H2O (205 mL) was purged with N2 for 1 h before the addition of Pd(PPh3)4 (9.2 g, 7.9 mmol). The mixture was further degassed with N2 for 5 min and then heated to 85° C. for 7 h under N2. Upon cooling, the reaction mixture was diluted with EA (250 mL), washed with water (200 mL) and brine (200 mL), and dried over MgSO4. The reaction mixture was filtered and concentrated to give beige solid. The crude product was purified by recrystallization from 20% EA/hexanes to afford 22 g (71%) of 2-fluoro-5-(thiazol-2-yl)benzonitrile THZ INT-1 as a pale yellow solid. LCMS-ESI (m/z) calculated for C10H5FN2S: 204.2; found 205.0 [M+H]+, tR=3.26 min. 1H NMR (400 MHz, CDCl3) δ 8.21-8.16 (m, 1H), 8.15-8.08 (m, 1H), 7.86-7.81 (m, 1H), 7.36-7.32 (m, 1H), 7.27-7.21 (m, 1H). 13C NMR (101 MHz, CDCl3) δ 164.31, 162.22, 143.73, 132.68, 131.28, 128.34, 119.94, 116.98, 113.10.

1. customThe mixture was further degassed with N2 for 5 min
2. temperatureUpon cooling
3. additionthe reaction mixture was diluted with EA (250 mL)
4. washwashed with water (200 mL) and brine (200 mL)
5. dry with materialdried over MgSO4
6. filtrationThe reaction mixture was filtered
7. concentrationconcentrated
8. customto give beige solid
9. customThe crude product was purified by recrystallization from 20% EA/hexanes

ORD record

ord-072563af10114a148169a8008480606f

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08507538B2