Hydrochloric Acid → 3,4-Dichloro-2-fluorotoluene

Temperatur

-78 °C

Under an argon atmosphere, to a solution (75 mL) of N,N,N′,N′-tetramethylethylenediamine (16.15 g) in dry tetrahydrofuran was added a solution (139 mL) of 1 mol/L-sec-butyllithium in hexane/cyclohexane under cooling (dry ice-acetone bath) at not higher than −60° C., and the mixture was stirred at the same temperature for 20 min. The mixture was further cooled to −78° C., and a solution (50 mL) of 4-chloro-2-fluoro-1-methylbenzene (18.26 g) in dry tetrahydrofuran was added thereto. After the reaction mixture was stirred at the same temperature for 30 min, a solution (275 mL) of hexachloroethane (119.6 g) in dry tetrahydrofuran was added dropwise thereto. The mixture was stirred at the same temperature for 30 min to gradually warm to room temperature. To the reaction mixture was added 6 mol/L hydrochloric acid to adjust to pH=5 and the mixture was concentrated. The residue was partitioned between ether and water, and the organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was placed on a glass filter, washed with a small amount of ether and filtrated. The filtrate was concentrated and evaporated under reduced pressure. The fraction at the boiling point of 48° C. (1.5 Torr) was collected to give the title compound as a colorless oil (yield: 19 g).

1. stirringAfter the reaction mixture was stirred at the same temperature for 30 min
2. stirringThe mixture was stirred at the same temperature for 30 min
3. temperatureto gradually warm to room temperature
4. concentrationthe mixture was concentrated
5. customThe residue was partitioned between ether and water
6. washthe organic layer was washed with saturated brine
7. dry with materialdried over anhydrous magnesium sulfate
8. concentrationconcentrated
9. filtrationfilter
10. washwashed with a small amount of ether
11. filtrationfiltrated
12. concentrationThe filtrate was concentrated
13. customevaporated under reduced pressure
14. customThe fraction at the boiling point of 48° C. (1.5 Torr) was collected

ORD-Eintrag

ord-fdecf1cdcc554862a3db0080801bfb11

Quelldatensatz

uspto-grants-2013_11

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08592452B2