Hydrochloric Acid → HCID 23565291, compound

Temperature

-90 °C

1.1 ml of dibromomethane was dissolved in tetrahydrofuran (20 ml) and cooled to −90° C. Into the solution thus obtained were dropped 9.77 ml of a 1.6 M solution of n-butyllithium in hexane and 20 ml of a solution of lithium 2,2,6,6-tetramethylpiperidide, which had been prepared from 2.88 ml of 2,2,6,6-tetramethylpiperidine, in tetrahydrofuran while maintaining the bulk temperature at 10° C. or below. 5 minutes thereafter, 10 ml of a solution of 1.0 g of ethyl (3-methyl-3-azabicyclo[3.3.1]non-1-yl)carboxylate in tetrahydrofuran was dropped thereinto. After 20 minutes, 0.8 ml of 2,2,6,6-tetramethylpiperidine was added thereto. 5 minutes thereafter, 23.7 ml of a 1.6 M solution of n-butyllithium in hexane was dropped thereinto and the resulting mixture was stirred. After 10 minutes, the reaction mixture was heated to 30° C. and stirred for 1 hour. Then the reaction mixture was quickly dropped into a solution of hydrogen chloride prepared from 25 ml of acetyl chloride and 250 ml of ethanol and stirred at room temperature for 14 hours. The reaction mixture was concentrated and an aqueous solution of potassium carbonate was added thereto followed by the extraction with ethyl acetate. The ethyl acetate layer was washed with water and a saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate. After concentrating under reduced pressure, the residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate) to thereby give 0.63 g of the title compound as a slightly yellow oily substance.

1. customInto the solution thus obtained
2. temperaturewhile maintaining the bulk temperature at 10° C. or below
3. waitAfter 10 minutes
4. temperaturethe reaction mixture was heated to 30° C.
5. stirringstirred for 1 hour
6. stirringstirred at room temperature for 14 hours
7. concentrationThe reaction mixture was concentrated
8. additionan aqueous solution of potassium carbonate was added
9. extractionthereto followed by the extraction with ethyl acetate
10. washThe ethyl acetate layer was washed with water
11. dry with materiala saturated aqueous solution of sodium chloride and dried over anhydrous sodium sulfate
12. concentrationAfter concentrating under reduced pressure
13. customthe residue was purified by silica gel column chromatography (eluted with n-hexane/ethyl acetate)

ORD record

ord-d0f0fb6b00a04391810b8ee041f0b8c4

Source dataset

uspto-grants-2003_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06518423B1