Methyl iodide → 9-(4-Chloro-benzenesulfonyl)-2-methyl-9-aza-bicyclo[3.3.1]nonan-3-one

Temperature

-78 °C

To a stirring mixture of 9-(4-chloro-benzenesulfonyl)-9-aza-bicyclo[3.3.1]nonan-3-one (550 mg, 1.75 mmol) in THF (2 mL) at −78° C. was added LiHMDS in THF (2.62 mL, 1.0 M in THF, 2.62 mmol) dropwise over 15 min. The resulting mixture was allowed to stir at −78° C. for 30 min before the addition of MeI (1.24 g, 8.75 mmol). The reaction mixture was stirred at −78° C. for 2.5 h before it was allowed to warm up to room temperature for 15 min. The reaction mixture was quenched by the addition of a saturated aqueous NH4Cl solution (25 mL) and EtOAc (25 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×25 mL). The combined organic layers were washed with brine, dried over MgSO4, filtered, and concentrated under reduced pressure. The crude mixture was purified via silica gel chromatography to give 9-(4-chloro-benzenesulfonyl)-2-methyl-9-aza-bicyclo[3.3.1]nonan-3-one as a white solid. Retention time (min)=2.13 min, Method [1], MS (ESI) 350 (M+Na).

1. temperatureto warm up to room temperature for 15 min
2. customThe reaction mixture was quenched by the addition of a saturated aqueous NH4Cl solution (25 mL) and EtOAc (25 mL)
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with EtOAc (2×25 mL)
5. washThe combined organic layers were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe crude mixture was purified via silica gel chromatography

ORD record

ord-6abf3921805f449a83b4f351482acbac

Source dataset

uspto-grants-2008_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07345056B2