o-Xylyl bromide → 1-(1,1-Dimethylethyl) 4-methyl 4-[(2-methylphenyl)methyl]-1,4-piperidinedicarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of N-t-butoxycarbonyl isonipecotic acid methyl ester (10.1 g 41.8 mmol) in 140 ml of dry THF at -78° C. was added LDA (59 ml of a 1.0M solution in THF, 59 mmol) over 15 min. The resulting orange solution was stirred at -78° C. for 1 hr and then treated dropwise with 2-methylbenzyl bromide (6.80 ml, 50.7 mmol) and then allowed to warm slowly to room temperature over 16 hrs. The reaction was quenched with saturated aqueous NH4Cl, diluted with H2O, and extracted with EtOAc. The combined organic extracts were washed with brine, and concentrated in vacuo to an orange gum. Chromatography (SiO2, eluting with 20 to 30% EtOAc in hexanes) and evaporation of solvent in vacuo, afforded the product as a white solid.

Provenance & Evidence