Sodium Hydroxide → 3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

3-(3-Hydroxy-phenyl)-piperidine-1-carboxylic acid tert-butyl ester (17.03 g, 61.39 mmol) was dissolved in 420 mL acetone in a 3-neck 1 L round bottom flask equipped with a mechanical stirrer. 1,1,1-trichloro-2-methyl-2-propanol hydrate (21.80 g, 122.78 mmol) was added and the solution was cooled to 0° C. Sodium hydroxide pellets (19.65 g, 491.12 mmol) were added to the solution at 0° C. over 4 h in four portions. The reaction mixture warmed to ambient temperature between additions and then recooled. Once the additions were complete, the reaction mixture was allowed to stir at ambient temperature for 24 h and then concentrated under reduced pressure. The resulting residue was taken up in water (500 mL), acidified with 6N aqueous hydrochloric acid, stirred 10 min and then extracted with ethyl acetate (3×300 mL). The combined organics were washed with saturated aqueous sodium chloride, dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure to provide 3-[3-(1-Carboxy-1-methyl-ethoxy)-phenyl]-piperidine-1-carboxylic acid tert-butyl ester as a brown oil which was taken on to the next step without further purification.

Provenance & Evidence