Methyl iodide → HCID 72299200, compound

Temperature

0 °C

To a solution of 170.7 ul (1.208 mmol) diisopropylamine in 4 ml THF were added 755 ul (1.208 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. Then 300 ul HMPA was added. A solution of 200 mg (0.805 mmol) (3SR,5RS)-1,3-dimethyl-5-nitro-5-phenyl-piperidin-2-one (example A.20, step a) in 2 ml THF was added dropwise. The brown solution was stirred at −70° C. for 45 minutes. 151 ul (2.415 mmol) methyliodide in THF (1 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 1 hour at 0° C., the mixture was quenched with 7 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 131 mg (62%) of the title compound as a yellow oil. MS (m/e): 263.2 (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 1 hour at 0° C.
6. customthe mixture was quenched with 7 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-b1b8debad1ff490899814c69f62bf66c

Source dataset

uspto-grants-2015_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09067911B2