Hydrochloric Acid → HCID 58695815, compound

Temperature

-78 °C

To a solution of diisopropylamine (0.471 g, 4.65 mmol) in anhydrous THF (10.0 mL) was added n-BuLi (2.91 mL, 4.65 mmol, 1.6 N in THF) at 0° C. The mixture was stirred at the temperature for 15 minutes and cooled to −78° C., followed by addition of a solution of 3-cyclohex-2-en-1-yl 8-ethyl 8-azabicyclo[3.2.1]octane-3,8-dicarboxylate (1-5) (1.30 g, 4.23 mmol) in THF (5.0 mL). After stirring at −78° C. for 30 min, TMSCl (0.459 g, 4.23 mmol) was added and the resulting solution was stirred at −78° C. for 1 h. The mixture was allowed to warm to room, temperature and stirred at 80° C. overnight. After cooling to room temperature, 2 N aqueous solution of HCl (10 mL) was added to the mixture. The mixture was stirred continued for 5 minutes, then partitioned between Et2O (50 mL) and 2 N HCl aqueous solution. The organic phase was washed with water, brine, dried over Na2SO4 and concentrated to give a crude residue. Purification of the crude residue by flash chromatography over silica gel (gradient elution; 10%-50% ethyl acetate/hexanes as eluent) afforded (1-6) as a white solid.

1. stirringAfter stirring at −78° C. for 30 min
2. stirringthe resulting solution was stirred at −78° C. for 1 h
3. temperatureto warm to room, temperature
4. stirringstirred at 80° C. overnight
5. temperatureAfter cooling to room temperature
6. stirringThe mixture was stirred
7. waitcontinued for 5 minutes
8. custompartitioned between Et2O (50 mL) and 2 N HCl aqueous solution
9. washThe organic phase was washed with water, brine
10. dry with materialdried over Na2SO4
11. concentrationconcentrated
12. customto give a crude residue
13. customPurification of the crude residue by flash chromatography over silica gel (gradient elution; 10%-50% ethyl acetate/hexanes as eluent)

ORD record

ord-dcffd17a794741b1a26d6eb0ad9a9305

Source dataset

uspto-grants-2007_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07276520B2