Ammonium Chloride → 1-Benzyl-4-(4-trifluoromethoxybenzoyl)piperidine

Temperature

-60 °C

1-Bromo-4-trifluoromethoxybenzene (5.3 g, 22.0 mmol) was dissolved in dry THF (70 ml) under a nitrogen atmosphere, and this solution was cooled to −60° C. n-Butyllithium (1.6 M) hexane solution (15 ml, 24.0 mmol) was added dropwise to the solution, and the mixture was allowed to reach a temperature of −30° C. and stirred for 1 hour. This mixture was cooled to −60° C. again, to which a solution of 1-benzylpiperidine-4-carboxylic acid N-methyl-N-methoxyamide (4.1 g, 15.6 mmol) prepared in Reference Example 147 in THF (10 ml) was added dropwise, and the mixture was stirred for 1 hour and then at 0° C. for 3 hours. The reaction mixture was poured into saturated ammonium chloride aqueous solution, and extracted with diethyl ether. The extract was washed with water and brine, dried over magnesium sulfate, and then filtered. The filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=4/1) to afford 1-benzyl-4-(4-trifluoromethoxybenzoyl)piperidine (4.8 g, yield 85%) as a pale yellow oil.

1. additionwas added dropwise to the solution
2. customa temperature of −30° C.
3. additionwas added dropwise
4. stirringthe mixture was stirred for 1 hour
5. waitat 0° C. for 3 hours
6. extractionextracted with diethyl ether
7. washThe extract was washed with water and brine
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered
10. concentrationThe filtrate was concentrated under reduced pressure
11. customThe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=4/1)

ORD record

ord-792e91b389a04a938c952870e908b73c

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07262212B2