Hexachloroethane → 2-Chloro-3,4-difluorobenzoic acid

To a mixture of N,N,N′,N′-tetramethylethylenediamine (8.40 mL) and tetrahydrofuran (75 mL) was added sec-butyllithium (1.0 mol/L cyclohexane solution, 55.7 mL) under an argon atmosphere at −78° C., and the mixture was stirred for 30 min. A mixture of 3,4-difluorobenzoic acid (4.00 g) and tetrahydrofuran (25 mL) was added dropwise to the reaction mixture at the same temperature over 30 min. After the reaction mixture was stirred for 30 min, a mixture of hexachloroethane (24.0 g) and tetrahydrofuran (40 mL) was added dropwise to the reaction mixture at the same temperature over 30 min. After stirring for 30 min while raising the temperature to room temperature, the reaction mixture was poured into water. The aqueous layer was washed with diisopropyl ether, acidified with 6 mol/L hydrochloric acid and extracted with diethyl ether. The organic layer was washed with brine, dried over anhydrous sodium sulfate, and concentrated. The obtained residue was washed with diethyl ether to give the title product as a solid (yield: 2.95 g).

1. additionwas added dropwise to the reaction mixture at the same temperature over 30 min
2. stirringAfter the reaction mixture was stirred for 30 min
3. additionwas added dropwise to the reaction mixture at the same temperature over 30 min
4. stirringAfter stirring for 30 min
5. washThe aqueous layer was washed with diisopropyl ether
6. extractionextracted with diethyl ether
7. washThe organic layer was washed with brine
8. dry with materialdried over anhydrous sodium sulfate
9. concentrationconcentrated
10. washThe obtained residue was washed with diethyl ether

ORD record

ord-7d7dfa92f2694134bf7991fdd3999aa0

Source dataset

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08592452B2