Adaptation of an Exothermic and Acylazide-Involving Synthesis Sequence to Microreactor Technology

作者：Rumi Luigi; Pfleger Christophe; Spurr Paul; Klinkhammer Uwe; Bannwarth Willi^*

来源：Organic Process Research & Development, 2009, 13(4): 747-750.

DOI：10.1021/op9000516

The original three-step batchwise synthesis of the pharmaceutical intermediate (IR,2S,4S)-(7-oxa-bicyclo[2.2.1]hept-2-yl)-carbamic acid ethyl ester (4) from (1R,2S,4S)-7-oxabicyclo[2.2.1]heptane-2-carboxyolic acid ethyl ester (1) encompassed a highly exothermic hydrazine quenching step as well as an acylazide intermediate. After appropriately modifying the reaction conditions, all three steps could be adapted to a microreactor system and a continuous process which permitted the desired carbamate 4 to be prepared under safe operating conditions in yields of 96%, 94%, and 84% for the three individual steps.

• 出版日期2009-8