Practical One-Pot Synthesis of N-(tert-Butoxycarbonyl)sulfamide from Chlorosulfonyl Isocyanate via N-(tert-Butoxycarbonyl)aminosulfonylpyridinium Salt

• DOI: 10.1021/op0499728
• Publication Date: 2004-05-21T04:44:00Z
• Authors: Toshiaki Masui; Mikio Kabaki; Hideaki Watanabe; Tatsuya Kobayashi; Yoshiyuki Masui
• Keywords: 01 natural sciences; 0104 chemical sciences

An efficient and practical process for the one-pot synthesis of N-(tert-butoxycarbonyl)sulfamide (4), a raw material for the aminosulfamoyl-containing side chain 3 of a novel carbapenem antibiotic doripenem hydrate (S-4661: 1), is described. In the previous process, chlorosulfonyl isocyanate was converted to N-(tert-butoxycarbonyl)aminosulfonyl chloride (7), an extremely unstable intermediate against moisture, which afforded the target compound 4 using liquid ammonia at cryogenic temperatures in 90% isolated yield. The use of liquid ammonia required cryogenic reaction temperatures because of heat generated from the highly exothermic reaction and the low boiling point of ammonia. In the improved process, the deactivation of the sulfonyl chloride 7 with pyridine at 0 °C afforded water-resistant N-(tert-butoxycarbonyl)aminosulfonylpyridinium salt (8) which was converted in situ to the target compound 4 in the presence of water at 0 °C in 90−96% isolated yields. Aqueous ammonia can be used, and no cryogenic ...