10.1016/S0040-4039(98)01905-4
The research aimed to introduce a fluorine atom into the structure of 3-[2-hydroxy-3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]quinazolin-2,4-(1H, 3H)-dione (4), a compound of interest due to its partial structure similar to previously studied compounds with pharmacological activities. The study explored the reaction of 4 with diethylaminosulfur trifluoride (DAST), expecting a straightforward fluorination. However, instead of the desired product, a 1,2-migration occurred, leading to the formation of N-[2-fluoro-3-[4-(2-methoxyphenyl)piperazin-1-yl]propyl]phthalimide (11a) in 13% yield and N-[2-fluoromethyl-2-[4-(2-methoxyphenyl)piperazin-1-yl]ethyl]phthalimide (11b) in 73% yield. The reaction was proposed to proceed through a spiro-aziridinium intermediate, resulting in an unexpected migration. This discovery provides a practical approach for the preparation of 1-fluoroethylamine derivatives and contributes to the understanding of DAST-induced migrations in chemical synthesis. Key chemicals used in the process included DAST, phthalimide, glycidol, 2-methoxyphenylpiperazine, hydrazine monohydrate, isatoic anhydride, and triphosgene.
Xi
