4-Bromo-2-(4-fluorophenyl)thiazole synthesis

Yield:1142196-38-0 450 mg

Reaction Conditions:

with tetrakis(triphenylphosphine) palladium⁽⁰⁾;sodium carbonate in 1,2-dimethoxyethane at 105; for 0.2 h;Inert atmosphere;Sealed tube;Microwave irradiation;Suzuki Coupling;

Steps:

16.1 Step 1.
Preparation of 4-bromo-2-(4-fluorophenyl)thiazole


Following a modified procedure (Bach, T.; Heuser, S. Tetrahedron Lett. 2000, 41, 1707), a mixture of 2,4-dibromothiazole (486 mg, 2.0 mmol), 4-fluorophenyl boronic acid (266 mg, 1.9 mmol), and aqueous 2.0 M Na₂CO₃ solution (2.3 mL, 4.6 mmol) in DME (6.8 mL) was sparged with Ar for 3 min. Tetrakis(triphenylphosphine)palladium(0) (150 mg) was added and the reaction mixture was sparged with Ar for 1 min.
The reaction was sealed and irradiated at 105° C. for 12 min in a microwave reactor.
The reaction mixture was partitioned with EtOAc (50 mL) and saturated aqueous NaHCO₃ solution (10 mL).
The layers were separated and the organic layer was washed with saturated aqueous NaHCO₃ solution (10 mL), brine (20 mL), dried (Na₂SO₄), and concentrated in vacuo.
The crude material was purified by column chromatography over silica gel to provide 450 mg of 4-bromo-2-(4-fluorophenyl)thiazole which was directly used in the next step without further purification: LCMS (m/z): 259.9 (MH⁺), t_R=1.08 min.

References:

US2013/210818,2013,A1 Location in patent:Paragraph 0375