Cesium carbonate → Methyl 4-[3'-fluoro-4'-(formylamino)-1,1'-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate

温度

80 °C

A suspension of 2-fluoro-4-iodophenylformamide (1.94 g, 7.35 mmol, prepared as described above), bis(pinacolato)diboron (1.86 g, 7.35 mmol), potassium acetate (2.16 g, 22.1 mmol), and palladium acetate (49.4 mg, 0.22 mmol) in N,N-dimethylformamide (50 mL) was degassed by bubbling a flow of argon through the mixture for 30 minutes. The mixture was then heated at 80° C. for 3 h. After the mixture was cooled to rt, methyl 4-(4-bromophenyl)-2,2-dimethyl-4-oxobutanoate (2.2 g, 7.4 mmol), tetrakis(triphenylphosphine)palladium(0) (254.8 mg, 0.22 mmol), and cesium carbonate (3.59 g, 11.0 mmol) were added, and the reaction mixture was heated at 80° C. for 16 h. The mixture was then cooled to rt and water was added. The mixture was extracted with ethyl acetate and the combined extracts were dried over sodium sulfate. The mixture was concentrated under reduced pressure and the crude was purified by flash chromatography (Biotage Flash 40M, 1:1 ethyl acetate/hexane) to afford methyl 4-[3′-fluoro-4′-(formylamino)-1,1′-biphenyl-4-yl]-2,2-dimethyl-4-oxobutanoate (1.2 g, 46%). LC-MS ret. time 2.80 min, m/z 358.1 (MH+); 1H NMR (300 MHz, DMSO-d6) δ 1.19 (s, 6H), 3.36 (s, 2H), 3.51 (s, 3H), 7.56 (d, 1H), 7.69 (dd, 1H), 7.82 (d, 2H), 7.99 (d, 3H), 8.21 (t), 10.25 (s, 1H).

1. customwas degassed
2. customby bubbling a flow of argon through the mixture for 30 minutes
3. temperatureAfter the mixture was cooled to rt
4. temperaturethe reaction mixture was heated at 80° C. for 16 h
5. temperatureThe mixture was then cooled to rt
6. extractionThe mixture was extracted with ethyl acetate
7. dry with materialthe combined extracts were dried over sodium sulfate
8. concentrationThe mixture was concentrated under reduced pressure
9. customthe crude was purified by flash chromatography (Biotage Flash 40M, 1:1 ethyl acetate/hexane)

ORDレコード

ord-2cdaf61949d6482f90619953faff2a79

出典データセット

uspto-grants-2006_08

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US07091228B2