1,4-Dioxane hydrochloride → 4-{1-(4-fluorophenyl)-2-[4-(4-naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-1-methyl-3,6-dihydro-2H-pyridine

0.49 g of 1-t-Butoxycarbonyl-4-{1-(4-fluorophenyl)-2-[4-(4-naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-3,6-dihydro-2H-pyridine was dissolved in 5 ml of methanol, and 20 ml of 4M hydrogen chloride/1,4-dioxane solution was added, followed by stirring at room temperature for 2 hours. The reaction solution was concentrated under reduced pressure, ethyl acetate was added to the residue, the mixture was washed with 1M aqueous sodium hydroxide solution and a saturated aqueous sodium solution. The organic layer was dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated under reduced pressure. The residue was dissolved in 5 ml of acetonitrile, and 340 μl of 37% formalin, 200 μl of acetic acid and 90 mg of sodium cyanoborohydride were added, followed by stirring at room temperature for an hour. The reaction solution was diluted with ethyl acetate and washed with a saturated aqueous sodium bicarbonate solution and a saturated aqueous sodium chloride solution. The organic layer was dried over anhydrous sodium sulfate. After removal of the drying agent by filtration, the filtrate was concentrated under reduced pressure. The residue was purified by a silica gel column chromatography (Chromatorex NH, hexane:ethyl acetate=2:1) to give 0.25 g of 4-{1-(4-fluorophenyl)-2-[4-(4-naphthalen-1-yl-butyl)piperazin-1-yl]-2-oxoethyl}-1-methyl-3,6-dihydro-2H-pyridine as an oil.

1. concentrationThe reaction solution was concentrated under reduced pressure, ethyl acetate
2. additionwas added to the residue
3. washthe mixture was washed with 1M aqueous sodium hydroxide solution
4. dry with materialThe organic layer was dried over anhydrous sodium sulfate
5. customAfter removal of the drying agent
6. filtrationby filtration
7. concentrationthe filtrate was concentrated under reduced pressure
8. dissolutionThe residue was dissolved in 5 ml of acetonitrile
9. addition340 μl of 37% formalin, 200 μl of acetic acid and 90 mg of sodium cyanoborohydride were added
10. stirringby stirring at room temperature for an hour
11. additionThe reaction solution was diluted with ethyl acetate
12. washwashed with a saturated aqueous sodium bicarbonate solution
13. dry with materialThe organic layer was dried over anhydrous sodium sulfate
14. customAfter removal of the drying agent
15. filtrationby filtration
16. concentrationthe filtrate was concentrated under reduced pressure
17. customThe residue was purified by a silica gel column chromatography (Chromatorex NH, hexane:ethyl acetate=2:1)

ORD-Eintrag

ord-cf31b82e56eb4a28bc225cada343f2dd

Quelldatensatz

uspto-grants-2005_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US06949552B2