Ethanol → HCID 86747425, compound

A slurry of 3-quinuclidinone hydrochloride (16.2 g, 100 mmoles) in ethanol (16.5 ml) and water (7 ml) was treated with sodium hydroxide (4.0 g, 100 mmoles) and stirred for 15 minutes. Separately, a cooled (0° C.) mixture of piperidine (15 ml, 150 mmoles), water (15 ml), and ethanol (10 ml) was treated with 37% aqueous formaldehyde (11.5 ml, 150 mmoles), and the mixture was stirred at room temperature for 15 minutes. The mixtures were combined, refluxed for 45 minutes, cooled, and diluted with petroleum ether (250 ml). The organic layer was separated and the aqueous solution was extracted with petroleum ether (100 ml). The combined organic layers were dried (MgSO4), concentrated in vacuo, and dissolved in methanol (100 ml). Hydroxylamine hydrochloride (7.7 g, 110 mmoles) was added, followed by 25% sodium methoxide/methanol (2.16 g, 10 mmoles), and the mixture was stirred for 18 hours. Additional 25% sodium methoxide (21.6 g, 100 mmoles) was added, and the methanol was removed in vacuo and replaced with water (100 ml). The suspension was filtered, and the solid was collected and dried. The filtrate was saturated with sodium chloride, extracted with methylene chloride (3×100 ml), and the combined extracts were dried (Na2SO4), concentrated in vacuo, and triturated from ether. The combined solids were recrystallized from 2-propanol to yield 4.1 g (17%) of voluminous white needles, mp 196°-198° C. (dec).

1. temperatureSeparately, a cooled
2. stirringthe mixture was stirred at room temperature for 15 minutes
3. temperaturerefluxed for 45 minutes
4. temperaturecooled
5. customThe organic layer was separated
6. extractionthe aqueous solution was extracted with petroleum ether (100 ml)
7. dry with materialThe combined organic layers were dried (MgSO4)
8. concentrationconcentrated in vacuo
9. dissolutiondissolved in methanol (100 ml)
10. stirringthe mixture was stirred for 18 hours
11. customthe methanol was removed in vacuo
12. filtrationThe suspension was filtered
13. customthe solid was collected
14. customdried
15. extractionextracted with methylene chloride (3×100 ml)
16. dry with materialthe combined extracts were dried (Na2SO4)
17. concentrationconcentrated in vacuo
18. customtriturated from ether
19. customThe combined solids were recrystallized from 2-propanol

ORD record

ord-c205caaeb0b9440c9d4029e69419787e

Source dataset

uspto-grants-1993_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05273972