Methyl iodide → HCID 71116591, compound

Participants

Reaction Conditions

Reaction Steps

LHMDS (2.2 mL, 2.16 mmol, 1.0 equiv, 1.0 M in THF) was added to an oven-dried flask under N2 and cooled to −78° C. A solution of 2-(4-methoxyphenyl)-2-azabicyclo-[2.2.2]octan-5-one (2-1, 500 mg, 2.16 mmol, 1.0 equiv) in anhydrous tetrahydrofuran (8.6 mL) was added dropwise via cannula, and the resulting mixture was allowed to stir for 20 min at −78° C. Following this duration, the enolate mixture was added via cannula to a solution of iodomethane (0.68 mL, 10.8 mmol, 5.0 equiv) in anhydrous tetrahydrofuran (2.2 mL). After 1 h, the reaction contents were removed from the −78° C. bath and allowed to gradually warm to RT. After 18 h, LCMS showed complete consumption of starting material. The reaction was quenched with saturated NH4Cl (15 mL), added to ethyl acetate (20 mL) and diluted with water (5 mL). The layers were separated and the aqueous layer was back-extracted with ethyl acetate (3×10 mL). The combined organics were dried over Na2SO4, filtered and concentrated in vacuo to give an orange solid. Purification by normal-phase HPLC (0-40% CH3CN:0.1% TFA in H2O) provided 7-1 as a pale yellow solid (inconsequential 1:1 mixture of diastereomers).

Provenance & Evidence