Sodium Carbonate → 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+), tR=1.08 min.

1. customwas sparged with Ar for 3 min
2. additionTetrakis(triphenylphosphine)palladium(0) (150 mg) was added
3. customthe reaction mixture was sparged with Ar for 1 min
4. customThe reaction was sealed
5. customirradiated at 105° C. for 12 min in a microwave reactor
6. customThe reaction mixture was partitioned with EtOAc (50 mL) and saturated aqueous NaHCO3 solution (10 mL)
7. customThe layers were separated
8. washthe organic layer was washed with saturated aqueous NaHCO3 solution (10 mL), brine (20 mL)
9. dry with materialdried (Na2SO4)
10. concentrationconcentrated in vacuo
11. customThe crude material was purified by column chromatography over silica gel

ORDレコード

ord-482cf916c01b4958b513d3918292cb28

出典データセット

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08865732B2