Methyl iodide → Tert-butyl 4-(3-(ethoxycarbonyl)phenyl)-3-methyl-2-oxopiperidine-1-carboxylate

Temperature

-78 °C

Potassium bis(trimethylsilyl)amide (14 g, 71 mmol) was mixed with 300 mL of THF in a 1000 mL flame-dried round bottomed flask and the resulting mixture was cooled to −78° C. tert-butyl 4-[3-(ethoxycarbonyl)phenyl]-2-oxopiperidine-1-carboxylate (22.5 g, 64.8 mmol) dissolved in 150 mL of THF was added slowly to the mixture, via an addition funnel, and the resulting reaction mixture was stirred at −78° C. for 30 min. Methyl iodide (12.1 mL, 195 mmol) was then added dropwise and the reaction mixture was allowed to stir at −78° C. for 4 h before being allowed to warm to room temperature overnight. The reaction was quenched with saturated ammonium chloride and extracted 3 times with ether. The combined ethereal layers were washed with brine and dried over MgSO4, filtered, and concentrated under reduced pressure. The product was purified by flash chromatography (10-20% EA/hexanes) to give 6.1 g of the trans racemate of tert-butyl 4-[3-(ethoxycarbonyl)phenyl]-3-methyl-2-oxopiperidine-1-carboxylate (26%).

1. customflame-dried round bottomed flask
2. additionwas added slowly to the mixture, via an addition funnel
3. customthe resulting reaction mixture
4. stirringto stir at −78° C. for 4 h
5. temperatureto warm to room temperature overnight
6. customThe reaction was quenched with saturated ammonium chloride
7. extractionextracted 3 times with ether
8. washThe combined ethereal layers were washed with brine
9. dry with materialdried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under reduced pressure
12. customThe product was purified by flash chromatography (10-20% EA/hexanes)

ORD record

ord-5baada8453b94abd92aa5e4f85451c65

Source dataset

uspto-grants-2009_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07598243B2