Active Pharmaceutical Ingredients APIs Synthesized with Phosgene

Active Pharmaceutical Ingredients (APIs) Synthesized with Phosgene 

Amprenavir [161814-49-9], antiviral, HIV protease inhibitor, 5. The key intermediate succinimido (S)-3-tetrahydrofuryl carbonate 4 [3-6] is synthesized with phosgene through (S)-3-tetrahydrofuryl chloroformate 2. 

Azlocillin [37091-66-0], antibiotic, 10. Phosgenation of 2-imidazolidinone 6 with phosgene in THF gives 1-chloroformyl-imidazolidinone 7, a key intermediate that forms the corresponding urea 9 upon reaction with d-(—)-a-phenylglycine 8 [7-9]. 

An improved phosgenation of N,N -disubstituted cyclic urea 6 to form 1-chloro-formyl-imidazolidinone 7, using phosgene in DCE at 80 °C (1 h, 86% yield) has been reported [8, 9]. 

Besides Ampicillin, 1-chloroalkyl alkyl carbonates, in particular 1-chloroethyl ethyl carbonate (CEEC), 1-chloroethyl isopropyl carbonate (CEIC), 1-chloroethyl cyclohexyl carbonate (CECC), and chloromethyl ethyl carbonate (CEMC), have been 

---