2-Chloroethyl chloroformate → 4-(4-Trifluoromethoxybenzoyl)-piperidine

1-Benzyl-4-(4-trifluoromethoxybenzoyl)piperidine (4.8 g, 13.2.2 mmol) prepared in Reference Example 148 was dissolved in methylene chloride (60 ml), and this solution was cooled in an ice-bath. 2-Chloroethyl chloroformate (2.9 ml, 26.4 mmol) was added dropwise to the solution, and the mixture was stirred at the same temperature for 30 minutes. The reaction mixture was concentrated under reduced pressure, methanol (100 ml) was added to the residue, and the resulting mixture was heated under reflux for 15 minutes. Water was added to the reaction mixture, which was stirred for 30 minutes, and neutralized with sodium hydroxide aqueous solution. The mixture was extracted with methylene chloride. The extract was washed with brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure, and the residue was purified by silica gel column chromatography(n-hexane/ethyl acetate=1/1) to afford 4-(4-trifluoromethoxybenzoyl)piperidine (1.3 g, yield 36%) as a pale orange-colored crystalline powder.

1. temperaturethis solution was cooled in an ice-bath
2. concentrationThe reaction mixture was concentrated under reduced pressure, methanol (100 ml)
3. additionwas added to the residue
4. temperaturethe resulting mixture was heated
5. temperatureunder reflux for 15 minutes
6. additionWater was added to the reaction mixture, which
7. stirringwas stirred for 30 minutes
8. extractionThe mixture was extracted with methylene chloride
9. washThe extract was washed with brine
10. dry with materialdried over magnesium sulfate
11. filtrationfiltered
12. concentrationThe filtrate was concentrated under reduced pressure
13. customthe residue was purified by silica gel column chromatography(n-hexane/ethyl acetate=1/1)

ORD record

ord-1aa0f1edf24445988349146b7cf1870a

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07262212B2