trans-4-tert-butoxy-5-hydroxycyclopent-2-en-1-one (5g, 29mmol)
tert-butyldimethylsilyl chloride (8.85g, 58mmol)
imidazole (4g, 58mmol)
dichloromethane (distilled from CaH₂, 100mL)

The alcohol (in this case a cyclopentenone) is stirred in dichloromethane at 0 ^oC and the TBS-Cl is added in one portion. The solution is stirred for 30 minutes, then the imidazole is added, and the reaction is stirred at 0 ^oC until all the starting material is consumed (TLC, 4-5 hours). The reaction is then quenched with sodium bicarbonate solution, extracted with ether, washed with brine, dried over magnesium sulphate, filtered and concentrated. Purification is by column chromatography eluting with 50% Et₂O/PE (only a short column should be required).

This is a good example of a silylation of a secondary alcohol. In this case, the alcohol would appear to be relatively unhindered and reactive (yields are 80-90%); some silylations take considerably longer, especially when protecting tertiary alcohols, which usually require the use of TBS-OTf. As shown in the example above, primary alcohols can be protected in the presence of secondary alcohols, although it is interesting to note the relative unreactivity of the primary alcohol in this case, a typical reaction taking 10 hours to complete,even in the presence of catalytic DMAP, as opposed to 4 hours for the secondary alcohol in the cyclopentenone. The solvent of choice in this instance is DCM, but DMF is frequently used, and sometimes gives better yields, though not in the examples shown. It is of course less convenient than DCM though.

¹H NMR (300MHz, CDCl₃) 7.23 (1H, dd, J=6.26, 1.7), 6.14 (1H,dd, J=6.26, 0.9), 4.56 (1H, d, J=1.2), 4.13 (1H, d, J=2.8), 1.3 (9H, s), 0.19 (3H, s), 0.14 (3H, s).

Greene W., Wuts P.G.M.,Protective groups in organic synthesis, Wliey Interscience 3rd Edition 1999