A short radiosynthesis of 6-[C3H3]-dorzolamide at very high specific activity and optical purity

6-[C 3 H 3 ]-Dorzolamide£# was prepared starting from N,N'-bis-Boc-6-desmethyldorzolamide. An efficient radiosynthesis was developed involving a regioselective and stereo-controlled 3 H-methylation of the α-sulfone carbanion in the presence of the monoprotected sulfonamide anion. The methylation led to a mixture (ca. 7 : 1 for 4S,6R : 4S,6S) of the diastereomeric, tritiated products. Removal of the Boc protecting groups followed by HPLC purification of the resulting diastereomers afforded 6-[C 3 H 3 ]-dorzolamide with > 99 % radiochemical purity, > 98.4 % enantiomeric excess, and a specific activity of > 74 Ci/mmol.