2-Butene, 1-bromo-3-methyl- → 1-Benzyl 3-ethyl 3-(3-methylbut-2-en-1-yl)piperidine-1,3-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 1-benzyl 3-ethyl piperidine-1,3-dicarboxylate (120.0 g, 0.412 mol) in THF (400 ml) cooled at −78° C. was added dropwise 270 mL of sodium bis(trimethylsilyl)amide solution (1M solution in THF from Aldrich, cat#:245585) over 2 h. The mixture was stirred at −78° C. for additional 1 h. Then 1-bromo-3-methylbut-2-ene (Aldrich cat #: 249904) (71 mL, 0.62 mol) was added slowly over 1 h. The mixture was stirred at −78° C. for 30 min, and allowed to warm to r.t. and stirred for an additional 3 h. The reaction mixture was quenched with 1N HCl aq. solution. Most of THF was removed under reduced pressure. The residue was extracted with ethyl acetate. The combined extracts were washed with sat. aq. NaHCO3 and brine, then dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by flash column chromatography on a silica gel column with 10˜20% ethyl acetate in hexane to yield the desired product (140 g, 94%). LC/MS: m/e=332.2 (M+H)+.

Provenance & Evidence