Hexachloroethane → 2,3-Dichloro-4-fluorobenzoic acid

sBuLi (97 mL, 126 mmol) was dissolved in tetrahydrofuran (THF) (200 mL) at −78° C. and TMEDA (19.02 mL, 126 mmol) was added. 3-chloro-4-fluorobenzoic acid (10 g, 57.3 mmol, commercially available from e.g. Sigma-Aldrich, Fluorochem or Apollo) dissolved in tetrahydrofuran (THF) (50 mL) was added dropwise at −78° C. and the solution stirred at this temperature for 30 minutes. Hexachloroethane (54.2 g, 229 mmol) dissolved in tetrahydrofuran (THF) (200 mL) was added dropwise and the solution stirred to room temperature over 4 hours. Water (25 mL) was added and the solution concentrated in vacuo. The residue was partitioned between diethyl ether (300 mL) and saturated sodium bicarbonate solution (50 mL) and extracted with saturated sodium bicarbonate solution (3×50 mL). The aqueous phase was acidified to pH1 with 5N hydrochloric acid, extracted with diethyl ether (3×200 mL), combined extracts dried over anhydrous magnesium sulfate and concentrated in vacuo to afford a crude solid (9.21 g). The crude solid was recrystalised from heptane/diethyl ether to afford the desired product in 4.91 g.

1. additionwas added dropwise at −78° C.
2. additionwas added dropwise
3. stirringthe solution stirred to room temperature over 4 hours
4. concentrationthe solution concentrated in vacuo
5. customThe residue was partitioned between diethyl ether (300 mL) and saturated sodium bicarbonate solution (50 mL)
6. extractionextracted with saturated sodium bicarbonate solution (3×50 mL)
7. extractionextracted with diethyl ether (3×200 mL)
8. dry with materialdried over anhydrous magnesium sulfate
9. concentrationconcentrated in vacuo
10. customto afford a crude solid (9.21 g)
11. customThe crude solid was recrystalised from heptane/diethyl ether

ORD record

ord-6af764148c6a41168af2f8f75a3241e5

Source dataset

uspto-grants-2013_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08501946B2