Sodium Hydroxide → 2,6-Dichloro-3-fluorobenzoic acid

To a cooled (−5° C.) solution of sodium hydroxide (252 g, 6.3 mol) in water (800 mL) was added bromine (86 mL, 1.68 mol) dropwise. The temperature of the reaction mixture was kept below −5° C. during the addition. A solution of 1-(2,6-Dichloro-3-fluorophenyl)ethanone (100 g, 480 mmol) in dioxane (800 ml) was added to the solution of sodium hypobromide in 1 h while maintaining the temperature below 0° C. The reaction mixture was warmed to room temperature and stirred for 2 h. After the TLC showed absence of starting material, the excess sodium hypobromide was destroyed with sodium sulfite (100 g in 100 mL water). The resulting solution was heated to 90° C. for 2 h. The reaction mixture was acidified with conc. HCl with vigorous stirring. The acidic solution was concentrated to remove all the dioxane and then extracted with dichloromethane (2×500 mL). The organic layer was dried (Na2SO4) and concentrated to give an oily residue, which after trituration with hexanes gave the title compound as a white solid. 1H NMR (CDCl3, 300 MHz): δ=7.20 (dd, 1H, J=8.7, 8.4 Hz), 7.33 (dd, 1H, J=9.3, 4.5 Hz).

1. additionThe temperature of the reaction mixture was kept below −5° C. during the addition
2. temperaturewhile maintaining the temperature below 0° C
3. customthe excess sodium hypobromide was destroyed with sodium sulfite (100 g in 100 mL water)
4. temperatureThe resulting solution was heated to 90° C. for 2 h
5. concentrationThe acidic solution was concentrated
6. customto remove all the dioxane
7. extractionextracted with dichloromethane (2×500 mL)
8. dry with materialThe organic layer was dried (Na2SO4)
9. concentrationconcentrated
10. customto give an oily residue, which after trituration with hexanes

ORD record

ord-eb1042ebd8c64a77bff93bedc5bcb08d

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592448B2