Benzyl Bromide → Ethyl-1-benzoyl-4-(phenylmethyl)-4-piperidinecarboxylate

Participants

Reaction Conditions

Reaction Steps

A stirred solution of 176 mL of commercial 1M lithium bistrimethylsilylamide in tetrahydrofuran was diluted with 100 mL of tetrahydrofuran and cooled to -78° C. under inert atmosphere. A solution of 44 g of ethyl 1-benzoyl-4-piperidinecarboxylate in 200 mL of tetrahydrofuran was added dropwise keeping the temperature below -60° C., followed by 21 mL of benzyl bromide. The resulting mixture was allowed to warm and stir overnight, diluted with 200 mL of 1N hydrochloric acid, 200 mL of ethyl acetate and separated. The organic layer was washed with 200 mL of 1N hydrochloric acid, dried over MgSO4, and concentrated. The residue was dissolved in 300 mL of toluene, filtered and concentrated under reduced pressure. Drying under reduced pressure gave 56.3 g of ethyl 1-benzoyl-4-(phenylmethyl)-4-piperidinecarboxylate as a viscous oil homogeneous by thin layer chromatography, eluting with 1:1 ethyl acetate: hexane, 1H NMR (300 MHz, CDCl3) 1.20 (t, 3H), 1.40 (m, 1H), 1.60 (m, 1H), 2.07 (m, 1H), 2.22 (m, 1H), 2.85 (d, 2H), 3.08 (m, 1H), 3.65 (m, 1H), 4.12 (q, 2H), 4.65 (m, 1H), 7.04 (m, 2H), 7.24 (m, 3H), 7.38 (m, 5H).

Provenance & Evidence