TBDMSCl

TBDMSCl, or tert-butyldimethylsilyl chloride, is a silylating reagent widely used in organic synthesis to convert alcohols (and sometimes amines) into their tert-butyldimethylsilyl ethers. The silicon center is bonded to two methyl groups, one tert-butyl group, and a chloride, giving the formula C6H15SiCl. The compound is typically moisture sensitive and used under strictly anhydrous conditions; it is commonly available as a solution in an organic solvent or in neat form.

In protection protocols, an alcohol is treated with TBDMSCl in the presence of a base such as imidazole or DIPEA in dry solvents like dichloromethane, DMF, or THF. A catalytic or catalytic-like amount of DMAP can be used to accelerate the reaction. Typical conditions are room temperature to 0 °C, with stoichiometry around 1.0–1.5 equivalents of TBDMSCl relative to the alcohol. The result is a stable tert-butyldimethylsilyl ether that tolerates many common reaction conditions, enabling stepwise synthesis and selective deprotections later in the sequence.

Deprotection of TBDMS ethers is usually achieved with fluoride sources, such as TBAF or HF-pyridine, or with some Brønsted acids under mild conditions. The silyl group is generally more easily removed than the corresponding TBDPS (tert-butyldiphenylsilyl) group, though deprotection conditions should still be chosen to avoid undesired side reactions.

Handling and safety considerations include moisture sensitivity and irritant/possible toxic effects of the reagent. Proper storage under inert gas or tightly closed containers, away from moisture, is advised, and appropriate personal protective equipment should be used when handling.