Thalidomide is racemic; while S-thalidomide is the bioactive form of the molecule, the individual enantiomers can racemize to each other due to the acidic hydrogen at the chiral centre, which is the carbon of the glutarimide ring bonded to the phthalimide substituent. The racemization process can occur in vivo. The process of conversion of one enantiomer to its mirror-image version with no other change in the molecule is called chiral inversion.
Celgene Corporation originally synthesized thalidomide using a three-step sequence starting with -glutamic acid treatment, but this has since been reformed by the use of -glutamine. As shown in the image below, N-carbethoxyphthalimide (1) can react with -glutamine to yield N-phthaloyl--glutamine (2). Cyclization of N-phthaloyl--glutamine occurs using carbonyldiimidazole, which then yields thalidomide (3). Celgene Corporations original method resulted in a 31% yield of S'-thalidomide, whereas the two-step synthesis yields 85–93% product that is 99% pure.