Methyl iodide → HCID 72299202, compound

Temperature

0 °C

To a solution of 1.6 ml (11.1 mmol) diisopropylamine in 40 ml THF were added 7 ml (11.1 mmol) of a 1.6M n-Buli solution in hexane at −5° C. The solution was stirred for 15 minutes at 0° C. and then cooled to −70° C. A solution of 2 g (8.538 mmol) rac-1-methyl-5-nitro-5-phenyl-piperidin-2-one (example A9, step 1) in 20 ml THF was added dropwise. The brown solution was stirred at −70° C. for 45 minutes. 639 ul (10.25 mmol) methyliodide in THF (8 ml) were added dropwise at −70° C. The mixture was stirred at −70° C. for 1 hour and then allowed to warm to 0° C. After 30 minutes at 0° C., the mixture was quenched with 30 ml of a 20% NH4Cl solution. Water and ethyl acetate were added. The aqueous layer was extracted once with ethyl acetate. The combined organic phases were dried over sodium sulfate, filtered and concentrated in vacuo. The crude product was purified on silica gel (Eluent: Heptane/ethyl acetate 0 to 100%) to provide 1.72 g (81%) of the title compound as a yellow oil. MS (m/e): 249.2 (M+H)

1. temperaturecooled to −70° C
2. stirringThe brown solution was stirred at −70° C. for 45 minutes
3. stirringThe mixture was stirred at −70° C. for 1 hour
4. temperatureto warm to 0° C
5. waitAfter 30 minutes at 0° C.
6. customthe mixture was quenched with 30 ml of a 20% NH4Cl solution
7. additionWater and ethyl acetate were added
8. extractionThe aqueous layer was extracted once with ethyl acetate
9. dry with materialThe combined organic phases were dried over sodium sulfate
10. filtrationfiltered
11. concentrationconcentrated in vacuo
12. customThe crude product was purified on silica gel (Eluent: Heptane/ethyl acetate 0 to 100%)

ORD record

ord-7c178233b75a4dab9cb1a737670c72e1

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067911B2