Formaldehyde → 2-Benzyl-2-aza-spiro[4.5]decane-4,4-dicarboxylic acid dimethyl ester hydrochloride

Participants

Reaction Steps

A solution of dimethyl (cyclohexylidene) malonate 2 (594 mg; 2.8 mmol), N-benzylglycine hydrochloride (1.41 g; 6.99 mmol), triethylamine (0.97 mL; 6.95 mmol), and paraformaldehyde (671 mg; 22.36 mmol) in benzene (18 mL) was slowly heated up to 125° C. (oil bath) (Dean-Stark). After stirring for 2 hours, the reaction mixture was cooled to room temperature, diluted with toluene (20 mL), and washed with brine. The aqueous phase was extracted with toluene (2×10 mL). The organic phases were combined, dried over MgSO4, and evaporated to give a brown oil which was purified on silica gel chromatography (EtOAc/heptane 1:3). The resulting pale yellow oil was diluted in diethyl ether (10 mL), and the compound was extracted with 2N HCl (2×5 mL). The aqueous phases were combined, washed with diethyl ether, and concentrated in vacuo to give 3 as a white solid (238 mg; 0.62 mmol; 22%).

Provenance & Evidence