Methyl iodide → HCID 45095121, compound

Participants

Reaction Conditions

Reaction Steps

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).

Provenance & Evidence