 |
|
Most Requested Journal Articles 4Q05-Chemistry and Related Science
Following is one of the journal articles most requested by researchers using CAS electronic products.
CAPLUS COPYRIGHT 2006 ACS on STN
A new, azide-free transformation of the key precursor epoxide 6 to the influenza neuraminidase inhibitor prodrug oseltamivir phosphate (1, Tamiflu) is described. This sequence represents a new and efficient transformation of an epoxide into a 1,2-diamino compd. devoid of potentially toxic and hazardous azide reagents and intermediates and avoids redn. and hydrogenation conditions. Using catalytic MgBr2.cntdot.OEt2 as a new, inexpensive Lewis acid, the introduction of the first amino function was accomplished by opening of the oxirane ring with allylamine followed by Pd/C-catalyzed deallylation to the amino alc. 16. The introduction of the second amino group was then accomplished via an efficient reaction cascade involving a domino sequence preferably utilizing a transient imino protection. Selective acetylation of the resulting diamine 17 was achieved under acidic conditions providing the cryst. 4-acetamido-5-N-allylamino-deriv. 18, which upon deallylation over Pd/C and phosphate salt formation afforded drug substance 1. The overall yield of this route from 6 of 35-38% exceeds the yield of the azide-based process (27-29%) and does not require any chromatog. purifn.
Updated 5/11/2007 12:24:15 PM
|
