1-(5-Bromo-2-chlorophenyl)-2-[methoxy(methyl)amino]ethanone → (5-Bromo-2-chloro-phenyl)-[4-(trifluoromethoxy)phenyl]methanone

Temperature

0 °C

To the solution of 1-(5-bromo-2-chlorophenyl)-2-[methoxy(methyl)amino]ethanone 15b (0.74 g, 2.65 mmol) in dry tetrahydrofuran (10 mL) was added bromo-[4-(trifluoromethoxy)phenyl]magnesium 15d afforded from the last step at 0° C. under N2. The resulting mixture was stirred at 0° C. for 4 hours. The reaction mixture was quenched with 20 mL of saturated brine, and then 20 mL of water and 40 mL of ethyl acetate were added in turn. The mixture was partitioned. The aqueous layer was extracted with ethyl acetate (20 mL×2). The combined organic layers were washed with saturated brine (20 mL×3), dried over anhydrous sodium sulfate and filtered. The filtrate was concentrated in vacuo and the residue was purified by silica gel chromatography eluted with PE/EtOAc(v/v)=50/1 to give the title compound 15e as a white solid (415 mg, 41.1%). The compound was characterized by the following spectroscopic data: 1H NMR (400 MHz, CDCl3) δ (ppm): 7.88 (d, 2H), 7.60 (dd, 1H), 7.53 (d, 1H), 7.37 (d, 1H), 7.33 (d, 2H).

1. customafforded from the last step at 0° C. under N2
2. customThe reaction mixture was quenched with 20 mL of saturated brine
3. addition20 mL of water and 40 mL of ethyl acetate were added in turn
4. customThe mixture was partitioned
5. extractionThe aqueous layer was extracted with ethyl acetate (20 mL×2)
6. washThe combined organic layers were washed with saturated brine (20 mL×3)
7. dry with materialdried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationThe filtrate was concentrated in vacuo
10. customthe residue was purified by silica gel chromatography
11. washeluted with PE/EtOAc(v/v)=50/1

ORD record

ord-1194052af1284f259846627a76be6a77

Source dataset

uspto-grants-2016_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09394329B2