Methyl iodide → Tert-butyl 4-[3-(benzyloxy)-2-methyl-3-oxopropyl]piperidine-1-carboxylate

Temperature

-78 °C

To a cooled (−78° C.) solution of 1.5M LDA/cyclohexane (6.48 mL, 9.73 mmol) in 50 mL of THF was added dropwise under a nitrogen atmosphere a solution of tert-butyl 4-[3-(benzyloxy)-3-oxopropyl]piperidine-1-carboxylate (2.60 g, 7.48 mmol) in 20 mL of THF. The resulting mixture was stirred at −78° C. for 45 min then was treated dropwise with neat iodomethane (1.40 mL, 22.4 mmol). After stirring at −78° C. for an additional 30 min, the reaction mixture was permitted to warm to rt and stir overnight. The reaction mixture was diluted with ether and washed in sequence with 1N HCl solution, saturated NaHCO3 solution, and brine. The ethereal layer was dried over anhydrous MgSO4, filtered, and concentrated. Purification by MPLC (silica, 25% ethyl acetate/hexanes) afforded tert-butyl 4-[3-(benzyloxy)-2-methyl-3-oxopropyl]piperidine-1-carboxylate.

1. stirringAfter stirring at −78° C. for an additional 30 min
2. temperatureto warm to rt
3. stirringstir overnight
4. washwashed in sequence with 1N HCl solution, saturated NaHCO3 solution, and brine
5. dry with materialThe ethereal layer was dried over anhydrous MgSO4
6. filtrationfiltered
7. concentrationconcentrated
8. customPurification by MPLC (silica, 25% ethyl acetate/hexanes)

ORD record

ord-ec997150e3c04227be761494aad27571

Source dataset

uspto-grants-2010_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07700591B2