NCAs are typically prepared by phosgenation of amino acids:
They were first synthesized by Hermann Leuchs by heating an N-ethoxycarbonyl or N-methoxycarbonyl amino acid chloride in a vacuum at 50-70 °C:
A moisture-tolerant route to unprotected NCAs employs epoxides as scavengers of hydrogen chloride.
This synthesis of NCAs is sometimes called the . The relatively high temperatures necessary for this cyclization results in the decomposition of several NCAs. Of several improvements, one notable procedure involves treating an unprotected amino acid with phosgene or its trimer.