Hydrochloric Acid → HCID 10727229, compound

A mixture of 8-(4-chlorophenyl)-1,4-dioxa-8-azaspiro[4.5]decane (2.6 g, 10.25 mmol), concentrated hydrochloric acid (12 ml), water (10 ml), and ethanol (50 ml) was heated under reflux for 5 hours. The reaction mixture was allowed to return to room temperature and concentrated under reduced pressure. To the residue 10% sodium hydroxide aqueous solution was added, and the mixture was extracted with methylene chloride. The extract was washed with water and brine, and dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was dissolved in methanol (50 ml), to which sodium borohydride (388 mg, 10.25 mmol) was added while cooling in an ice-bath, and the mixture was stirred for 30 minutes. To the reaction mixture, 10% hydrochloric acid was added, and the mixture was concentrated under reduced pressure. Saturated sodium bicarbonate aqueous solution was added to the residue, and the mixture was extracted with methylene chloride. The extract was washed with water and brine, and was dried over magnesium sulfate. After filtration, the filtrate was concentrated under reduced pressure. The residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/1) to afford 1-(4-chlorophenyl)piperidin-4-ol (1.73 g, yield 80%) as a pale yellow crystalline powder.

1. temperaturewas heated
2. temperatureunder reflux for 5 hours
3. customto return to room temperature
4. concentrationconcentrated under reduced pressure
5. additionTo the residue 10% sodium hydroxide aqueous solution was added
6. extractionthe mixture was extracted with methylene chloride
7. washThe extract was washed with water and brine
8. dry with materialdried over magnesium sulfate
9. filtrationAfter filtration
10. concentrationthe filtrate was concentrated under reduced pressure
11. additionwas added
12. temperaturewhile cooling in an ice-bath
13. concentrationthe mixture was concentrated under reduced pressure
14. additionSaturated sodium bicarbonate aqueous solution was added to the residue
15. extractionthe mixture was extracted with methylene chloride
16. washThe extract was washed with water and brine
17. dry with materialwas dried over magnesium sulfate
18. filtrationAfter filtration
19. concentrationthe filtrate was concentrated under reduced pressure
20. customThe residue was purified by silica gel column chromatography (n-hexane/ethyl acetate=3/1)

ORD record

ord-4266849952bc4d078acfc4b50a276ce2

Source dataset

uspto-grants-2007_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07262212B2