Methyl iodide → HCID 45095121, compound

Temperature

-30 °C

In an argon-dried 50 mL 3-neck round bottom flask fitted with a magnetic stirring bar, thermometer and septa with argon inlet, anhydrous THF (20 mL) and DIPEA (0.84 mL, 6 mmol, 1.2 eq) were introduced consecutively. The mixture was cooled to −30° C. and 1.6 M n-BuLi solution (3.75 mL, 6 mmol, 1.2 eq) was added dropwise via syringe. After 30 min stirring at −30° C. the in situ generated LDA solution was cooled to −76° C. and HMPA (1.3 mL, 7.5 mmol, 1.5 eq) was added, followed by a solution of 2-methyl-6-piperidinyl-1-ylbenzonitrile (6a, 1.0 g, 5 mmol) in THF (5 mL) which caused a dark coloration of the reaction mixture. The reaction was stirred at −76° C. for 2 h and MeI (0.4 mL, 6.5 mmol, 1.3 eq) was added. Immediately the dark brown solution became slightly yellow, indicating that the alkylation reaction was complete. The reaction was allowed to warm up to RT, quenched with saturated NH4Cl solution (20 mL) and the product was extracted with diethyl ether (3×30 mL). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate and the solvent was removed under reduced pressure. The crude product was purified by flash chromatography (eluted with 5% EtOAc in hexane) to give pure 2-ethyl-6-piperidin-1-ylbenzonitrile (6b, 0.88 g, 82% yield).

1. customIn an argon-dried 50 mL 3-neck round bottom flask
2. customfitted with a magnetic stirring bar
3. customthermometer and septa with argon inlet
4. temperaturewas cooled to −76° C.
5. stirringThe reaction was stirred at −76° C. for 2 h
6. customindicating that the alkylation reaction
7. temperatureto warm up to RT
8. customquenched with saturated NH4Cl solution (20 mL)
9. extractionthe product was extracted with diethyl ether (3×30 mL)
10. washThe combined organic extracts were washed with brine
11. dry with materialdried over anhydrous sodium sulfate
12. customthe solvent was removed under reduced pressure
13. customThe crude product was purified by flash chromatography (eluted with 5% EtOAc in hexane)

ORD record

ord-c8b3b60182be4634bff00471fb258348

Source dataset

uspto-grants-2009_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07582766B2