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

Participants

Reaction Conditions

Reaction Steps

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.

Provenance & Evidence