OMG! We Made One Gram of Remdesivir!


In this case, chemical compounds 14 and 15 (you don’t want to know their chemical names) are combined to form compound 16, which is the desired product. The letters (a,b) above the arrow show the reagents used to make the reaction work. In this case, it means that either reagent a or b may be used for this particular reaction. Let’s just stick to reagent (a):

(a) n-BuLi, (TMS)Cl, THF, – 78 °C, 25%

What does this gibberish mean? n-BuLi is short for n-butyllithium, which bursts into flame if exposed to oxygen or water. (TMS)Cl is short for trimethylsilyl chloride, another charmer, which also reacts like a madman with water and will cheerfully eat your skin. THF is short for the tetrahydrofuran, the solvent used. The -78ºC is the temperature (-108° F) at which the reaction is run. (4)

Some reactions have to be run at very low temperatures. This is one of them. If you mix this stuff together at room temperature your internal organs would be found in several time zones. 25% is the yield of the reaction – the weight of the product obtained from the reaction divided by the expected weight if the reaction went perfectly. Clearly, this one is very far from perfect; you’re losing 75% of your material. (5)

This might not be so awful if you could purchase 14 and 15, but this may or may not be possible. It could be that it took you a month to make them, in which case life begins to suck.


The remdesivir sequence consists of five reactions. Let’s assume that the yield of each is 90%, which is excellent. By the time you are done, you will have (0.9)5, or a 59% overall yield, meaning that you have thrown away 41% of the material. No such luck here. Here are the real numbers for the reactions in Scheme 1: 0.25 x 0.58 x 0.74 x 0.21 x 0.23 = .005 (0.05%). The average yield of the five steps is 36%, making the overall yield a god-awful 0.5%.

Second-Generation Synthesis

Without further torturing you with details, the second-generation synthesis consists of six reactions instead of five, but overall, life is much better. The yields of the six steps (not shown) are 40%, 85%, 86%, 90%, 70%, and 69% – an average of 73% per step. This makes the overall yield: 0.40 x 0.85 x 0.86 x 0.90 x 0.70 x 0.69 = 12.7% (25-times more efficient than Scheme 1. That’s a VERY big difference.