Methyl iodide → 1-(4-Tert-butyl-phenyl)-4-methyl-piperidine-4-carboxylic acid ethyl ester

Temperature

0 °C

Diisopropylamine (113 μL, 0.81 mmol) was diluted with tetrahydrofuran (1 mL). The resulting solution was cooled to 0° C., and a solution of n-butyllithium in cyclohexane (400 μL, 2M, 0.80 mmol) was then added. The mixture was stirred at 0° C. for 30 min. The mixture was then cooled to −78° C., and a solution of the 1-(4-Tert-butyl-phenyl)-piperidine-4-carboxylic acid ethyl ester (118 mg, 0.41 mmol, prepared in accordance with Example 48) in tetrahydrofuran (3 mL) was added. After 30 min, methyl iodide (57 μL, 0.41 mmol) was added. Afterward, the mixture was maintained at −78° C. for 1 hr. The mixture was then allowed to increase to room temperature, and maintained at that temperature for 1 hr. The mixture was then quenched with saturated aqueous ammonium chloride (15 mL). The organic phase was extracted with ethyl acetate (20 mL). The organic phase was then dried over magnesium sulfate, filtered, and concentrated under vacuum. The desired product was isolated as an oil (155 mg, quantitative yield).

1. temperatureThe mixture was then cooled to −78° C.
2. waitAfter 30 min
3. temperatureAfterward, the mixture was maintained at −78° C. for 1 hr
4. temperatureto increase to room temperature
5. temperaturemaintained at that temperature for 1 hr
6. customThe mixture was then quenched with saturated aqueous ammonium chloride (15 mL)
7. extractionThe organic phase was extracted with ethyl acetate (20 mL)
8. dry with materialThe organic phase was then dried over magnesium sulfate
9. filtrationfiltered
10. concentrationconcentrated under vacuum

ORD record

ord-2eb097c0e9de49fd89dbdd99174a333f

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08569495B2