4-Piperidinecarboxylic acid → 1-Carbobenzoxy-4-piperidinecarboxylic Acid

Participants

Reaction Steps

A solution of isonipecotic acid (12.9 g, 100 mmol) in 2N NaOH (55 mL) was cooled to 0° C. in an ice-bath. Benzylchloroformate (15.7 mL, 110 mmol, 1.1 eq.) and 2N NaOH (55 mL) were then added in about 10 portions, alternatively. The reaction mixture remained distinctly alkaline. The temperature of the reaction mixture was kept between 5 and 10° C. by controlling the rate of addition of reactants (about 45 min). The ice-bath was removed and the mixture was stirred at room temperature for 30 min. TLC showed the reaction was completed. The alkaline solution was extracted with Et2O (4×50 mL). The aqueous layer was acidified using 6N HCl to pH ˜5, extracted with EtOAc (3×100 mL). The combined EtOAc extracts were washed with saturated brine (100 mL), dried over Na2SO4, filtered and concentrated by rotary evaporation to give 1-benzyloxycarbonyl-piperidine-4-carboxylic acid as a white solid (17.3 g, 66 mmol, 66%). 1H NMR (300 MHz, CDCl3): δ 7.35 (m, 5H), 5.14 (s, 2H), 4.12 (m, 2H), 2.97 (t, 2H), 2.53 (m, 1H), 1.95 (m, 2H), 1.68 (m, 2H).

Provenance & Evidence