Hexachloroethane → HCID 58604077, compound

Temperature

40 °C

A solution of N,N,N′-trimethylethylenediamine (20.3 mL, 156 mmol) in 75 mL of THF was cooled to −50° C. and a 2.5M solution of n-butyllithium in hexanes (62.5 mL, 156 mmol) was added dropwise with stirring during 15 minutes, keeping the internal temperature below −35° C. The temperature was maintained at 40° C. for 30 minutes, and then the reaction mixture was cooled to −70° C. A solution of 4-fluoro-3-methoxybenzaldehyde (24.09 g, 156.3 mmol) in 75 mL of THF was added dropwise during 15 minutes, keeping the reaction temperature below −50° C. When the addition was complete, the reaction was allowed to warm to −40° C. and held there for 25 minutes. The reaction was then re-cooled to −70° C. and a 2.5M solution of n-butyllithium in hexanes (62.5 mL, 156 mmol) was added dropwise. When the addition was complete, the reaction was allowed to warm to −20° C. and kept at that temperature overnight (12 hours). The reaction mixture was then cooled to −30° C. and the cold solution was added via cannula during 30 minutes to a room temperature solution of hexachloroethane (111 g, 469 mmol) in 200 mL of THF. After stirring at room temperature for 4 hours, the reaction mixture was poured into 500 mL of ice cold 4N HCl. Most of the THF was removed by rotary evaporation under reduced pressure and the residual mixture was extracted twice with 1:1 ethyl ether/hexanes. The organic layers were combined and washed successively with 1N NaOH, 1N HCl, water, and brine. After drying over sodium sulfate, removal of the solvent under vacuum gave a yellow solid. Flash chromatography on silica gel eluting with hexanes/dichloroethane (2:1 to 1:1) gave 2-chloro-4-fluoro-3-methoxybenzaldehyde as a white solid.

1. customthe internal temperature below −35° C
2. temperaturethe reaction mixture was cooled to −70° C
3. customthe reaction temperature below −50° C
4. additionWhen the addition
5. temperatureto warm to −40° C.
6. waitheld there for 25 minutes
7. temperatureThe reaction was then re-cooled to −70° C.
8. additionWhen the addition
9. temperatureto warm to −20° C.
10. customkept at that temperature overnight (12 hours)
11. temperatureThe reaction mixture was then cooled to −30° C.
12. stirringAfter stirring at room temperature for 4 hours
13. customMost of the THF was removed by rotary evaporation under reduced pressure
14. extractionthe residual mixture was extracted twice with 1:1 ethyl ether/hexanes
15. washwashed successively with 1N NaOH, 1N HCl, water, and brine
16. dry with materialAfter drying over sodium sulfate, removal of the solvent under vacuum
17. customgave a yellow solid

ORD record

ord-1068d9633b6d40978a705a74a8c60bb2

Source dataset

uspto-grants-2008_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07432284B2