3-Quinuclidinol, (-)- → 1-Phenyl-cycloheptanecarboxylic acid (R)-(1-aza-bicyclo[2.2.2]oct-3-yl)ester

A solution of (R)-(3)-quinuclidinol (10.13 g) and 1-phenyl-cycloheptanecarboxylic acid methyl ester (Example 14d) (9.25 g) in toluene (90 mL) was heated to reflux with a Dean-Stark trap for 30 min. The reaction mixture was allowed to cool to room temperature and the trap was removed. Sodium hydride (60% dispersion in mineral oil) (3.19 g) was added portionwise under nitrogen and the reaction mixture was heated to reflux overnight under nitrogen. The reaction mixture was cooled in an ice bath and diluted with ethyl acetate (200 mL) and water (200 mL). The mixture was filtered and the layers separated. The aqueous layer was extracted with ethyl acetate (2×250 mL) and the combined organic layers were washed with brine, dried over magnesium sulfate and evaporated to give the crude product which was purified by silica gel chromatography eluting with EtOAc containing 1% triethylamine to give the sub-titled compound as a colourless oil (7.63 g)

1. temperatureto reflux with a Dean-Stark trap for 30 min
2. customthe trap was removed
3. additionSodium hydride (60% dispersion in mineral oil) (3.19 g) was added portionwise under nitrogen
4. temperaturethe reaction mixture was heated
5. temperatureto reflux overnight under nitrogen
6. temperatureThe reaction mixture was cooled in an ice bath
7. additiondiluted with ethyl acetate (200 mL) and water (200 mL)
8. filtrationThe mixture was filtered
9. customthe layers separated
10. extractionThe aqueous layer was extracted with ethyl acetate (2×250 mL)
11. washthe combined organic layers were washed with brine
12. dry with materialdried over magnesium sulfate
13. customevaporated
14. customto give the crude product which
15. customwas purified by silica gel chromatography
16. washeluting with EtOAc containing 1% triethylamine

ORD record

ord-b8c718e7b409472788a0573491ab546f

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08329729B2