It is a safer replacement for diazomethane, which is a sensitive explosive gas, whereas trimethylsilyldiazomethane is a relatively stable liquid and thus easier to handle.

Under these conditions, diazomethane itself is generated in situ as the active methylating agent, by an acid-catalyzed reaction between trimethylsilyldiazomethane and the alcohol with trimethylsilyldiazomethane as byproduct:[7] When the methanol is omitted, substantial amounts of trimethylsilyl ester and trimethylmethyl ester products are formed as well.

From it can be prepared other trimethylsilyldiazoalkanes: (CH3)3SiCLiN2 reacts with ketones and aldehydes to give, depending on the substituents, acetylenes.

[9] It has also been employed widely in tandem with GC-MS for the analysis of various carboxylic compounds which are ubiquitous in nature.

It has been implicated in the death of at least two chemists, a pharmaceutical worker in Windsor, Nova Scotia and one in New Jersey.