2-(Trimethylsilyl)ethoxymethyl chloride (SEM-Cl) is an organochlorine compound with the formula C6H15ClOSi, which was developed by Bruce H. Lipshutz during his work on the synthesis of N-methylmaysenine.

It is used to protect hydroxyl groups, which can be cleaved with fluoride in organic solvents selectively under mild conditions.

[1] Typically tetrabutylammonium fluoride and caesium fluoride can be used as deprotection reagents.

Alternatives such as magnesium bromide,[2] lithium tetrafluoroborate and boron trifluoride etherate were also developed to deprotect SEM group.

[3]