The first reported synthesis[2] of tetrolic acid is believed to be by German chemist Johann Georg Anton Geuther in 1871 as part of his work investigating the derivatives of ethyl acetoacetate.

Tetrolic acid is manufactured[3] on a commercial scale by treatment of propyne with a strong base (to form an acetylide), followed by carbon dioxide: Strong bases such as n-BuLi[4] and NaNH2[5] can be used.

Tetrolic acid is highly soluble in polar solvents (water, ethanol) and can be recrystallized from non-polar solvents (such as heptane, hexane or toluene).

Tetrolic acid sublimes at temperatures above 20°C, and should ideally be stored in a sealed container in a refrigerator.

[7] Accelerated rate calorimetry (ARC) showed exothermic onset from 135 °C, precluding short-path distillation as a means of purification.