Tetrahydrofuran → 1-(2-Bromo-5-fluorophenyl)ethan-1-one

To a solution of 2-bromo-5-fluoro-N-methoxy-N-methylbenzamide (1.54 g, 5.88 mmol) in THF (60 mL) at 0° C. was added McMgI (3.0 M in diethyl ether, 1.998 mL, 5.99 mmol) dropwise over 5 min, the reaction immediately turned bright yellow after a few drops and then after continued addition the reaction lost the yellow color and a significant amount of white precipitate crashed out. After 15 min the reaction was warmed to room temperature and stirred for 15 h after which an additional 3×0.5 equiv. McMgI (1.0 mL) was added every 3 h until after 23 h the reaction was quenched by addition of sat. aq. NH4Cl solution and extracted with diethy ether (3×). The combined organic layers were dried over anhydrous MgSO4, filtered and concentrated in vacuo and the resulting crude material was purified by column chromatography (SiO2, 0-20% EtOAc/Hexanes) to afford 1-(2-bromo-5-fluorophenyl)ethanone (1.038 g, 4.78 mmol, 81% yield). 1H NMR (400 MHz, CDCl3) δ ppm 7.57 (dd, J=8.8, 4.9 Hz, 1H), 7.18 (dd, J=8.4, 3.1 Hz, 1H), 7.07-6.99 (m, 1H), 2.63 (s, 3H).

1. customthe reaction immediately turned bright yellow after a few drops
2. additionaddition the reaction
3. additionMcMgI (1.0 mL) was added every 3 h until after 23 h the reaction
4. customwas quenched by addition of sat. aq. NH4Cl solution
5. extractionextracted with diethy ether (3×)
6. dry with materialThe combined organic layers were dried over anhydrous MgSO4
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customthe resulting crude material was purified by column chromatography (SiO2, 0-20% EtOAc/Hexanes)

ORD record

ord-7551c4769930477c8d3ac814494d50e5

Source dataset

uspto-grants-2016_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09321746B2