Sodium Hydroxide → 1-[(Benzyloxy)carbonyl]-4-methylpiperidine-4-carboxylic acid

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Reaction Conditions

Reaction Steps

4-Methyl-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (2.71 g, 10 mmol) is heated with 6M aq. HCl (20 mL) at 95° C. for 2 days. The mixture is cooled, basified with 33% aq. NaOH (ice bath cooling) and extracted with ether (2×50 mL). A spatula of NaH2PO4 is added, then the pH adjusted to 7 with conc. aq. HCl, CH2Cl2 (50 Vol %) is added and the mixture cooled at 0° C. Carbonic acid benzyl ester 2,5-dioxo-pyrrolidin-1-yl ester (1.508 g, 5 mmol) is added to the strongly stirred biphasic system and the mixture is stirred for 2 h. The pH is adjusted to 14 with aq. NaOH (1M) and the phases are separated. The aq. phase is extracted with CH2Cl2 (2×50 mL), the organic extracts are discarded. The pH is adjusted to 2 and the mixture is extracted with CHCl3 (4×50 mL). The organic extracts are dried (Na2SO4), filtered and evaporated to provide the title compound.

Provenance & Evidence