Hydrogen Bromide → 2-Bromo-1-(4-iodophenyl)ethanone

To a clear dark solution of 1-(4-iodophenyl)ethanone (1.046 kg, 4.251 mol, 1 equiv.) in DCM (8 L) was charged (dropwise) bromine (228 ml, 4.45 mol, 1.047 equiv.) over the period of 30 to 45 min at the ambient temperature. The reaction was slightly exothermic (temperature increased to about 20˜25° C.) and released a lot of hydrogen bromide gas as the by-product. The reaction was considered as complete after 3 to 4 hrs as indicated by HPLC (typically ˜7% starting material, ˜10% di-bromo by-product, and ˜83% desired mono-bromo product, all in area % by HPLC). It was then quenched and neutralized by aqueous NaHCO3 solution wash (4 L), followed by brine wash (3 L). Upon drying over Na2SO4, it is rotavapped and solvent swapped to THF and the desired product was crystallized from THF (final volume about 2 L) at from 50° C. to 20° C. to afford the 1st crop: 340 g (98% HPLC purity); by concentrating the mother liquor to about half-volume to afford the 2nd crop: 426 g (98% HPLC purity); by further concentrating and addition of hexanes (i.e., THF/hexanes, 1:1) to afford the 3rd crop: 339 g (97+% HPLC purity). The combined crystal title compound was 1.105 kg (80% yield). 1H NMR (500 MHz, CDCl3): 7.88 (d, 2H), 7.70 (d, 2H), 4.42 (s, 2H).

1. temperature(temperature increased to about 20˜25° C.)
2. customcomplete after 3 to 4 hrs
3. customIt was then quenched
4. washwash (4 L)
5. washwash (3 L)
6. dry with materialUpon drying over Na2SO4, it
7. customthe desired product was crystallized from THF (final volume about 2 L) at from 50° C. to 20° C.
8. customto afford the 1st crop
9. concentrationby concentrating the mother liquor to about half-volume
10. customto afford the 2nd crop
11. concentrationby further concentrating
12. additionaddition of hexanes (i.e., THF/hexanes, 1:1)
13. customto afford the 3rd crop

ORD record

ord-420b6d944f00466f8de2c1c660eb57bf

Source dataset

uspto-grants-2014_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08921573B2