Methyl phenylacetate → Tert-butyl 4-(3-oxo-4-phenylbutanoyl)piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

4-Acetyl-piperidine-1-carboxylic acid tert-butyl ester (1.00 g) was dissolved in anhydrous THF (6 mL) and cooled to 0° C. To this was added a solution of lithium hexamethyldisilazane (1.0M in hexanes; 4.84 mL). This was left to stir at 0° C. for 10 minutes before addition of a THF solution (2 mL) of methyl phenylacetate (0.661 g). The reaction mixture was left to stir for a total of 4 hours before being quenched by the addition of 1M aqueous HCl (50 mL). The reaction mixture was extracted with Et2O (3×75 mL) then the combined organic extracts were dried over magnesium sulfate and filtered. Evaporation of solvents under reduced pressure gave a thick yellow oil which was purified by column chromatography on silica gel, using an increasingly polar gradient of Et2O in DCM as eluent. Evaporation of solvents under reduced pressure gave the desired 4-(3-oxo-4-phenyl-butyryl)-piperidine-1-carboxylic acid tert-butyl ester as a clear oil (0.225 g); NMR (CDCl3): 1.45 (s, 9H), 1.54 (m, 2H), 1.76 (d, 2H), 2.28 (tt, 1H), 2.71 (br t, 2H), 3.61 (s, 2H), 4.12 (br d, 2H), 5.44 (s, 1H), 7.12-7.36 (m, 5H), 15.30 (s, 1H); MS: 344 (M−1−).

Provenance & Evidence