US EPA

7484612 

Journal Article 

Reactions of t -Boc-Protected Amines with Difluorocarbene 

Gerasov, A; Shivanyuk, A; Fetyukhin, V; Lukin, O 

2019 

1 

Synthesis
ISSN: 0039-7881
EISSN: 1437-210X 

Georg Thieme Verlag 

51 

12 

2579-2583 

English 

10.1055/s-0037-1610703 

WOS:000471236800015 

The reactions of t -Boc-protected secondary and primary amines with difluorocarbene generated from trimethylsilyl (fluorosulfonyl)difluoroacetate [Me 3 SiOC(O)CF 2 SO 2 F] (TFDA) in toluene at 110°C results in the replacement of t -Bu by difluoromethyl in the t -Boc group. This reaction can be carried out in the presence of CH 2 Br and COOMe moieties in the structure of the protected amine. In the example of a t -Boc-protected amine containing a C=C double bond, replacement of the t -Bu group and/or cyclodifluoropropanation takes place. Difluoromethyl esters are shown to react with primary and secondary amines yielding the corresponding ureas. © 2019 Georg Thieme Verlag. All rights reserved. 

acylation; difluoromethylcarbamate; t -Boc group; t -Bu/CHF 2 replacement; trimethylsilyl (fluorosulfonyl)difluoroacetate; urea; Acylation; Metabolism; Silicon compounds; Urea; BOC Group; Difluorocarbene; difluoromethylcarbamate; Double bonds; Primary and secondary amine; Secondary and primary amines; t -Bu/CHF2 replacement; Trimethylsilyl; Amines; (4 benzylpiperidin 1 yl)(pyrrolidin 1 yl)methanone; 1 (difluoromethyl) 4 methyl piperidine 1,4 dicarboxylate; amine; carbonyl derivative; chemical compound; difluorocarbene; difluoromethyl (3 bromopropyl)carbamate; difluoromethyl 2'2 difluoro 3' phenyl 8 azaspiro[bicyclo[3.2.1]octane 3,1' cyclopropane] 8 carboxylate; difluoromethyl 3 benzylidene 8 azabicyclo[3.2.1]octane 8 carboxylate; difluoromethyl 4 benzylpiperidine 1 carboxylate; difluoromethylcarbamate; n,4 dibenzylpiperidine 1 carboxamide; tert butyl 2',2' difluoro 3' phenyl 8 azaspiro[bicyclo[3.2.1]octane 3,1' cyclopropane] 8 carboxylate; tert butyloxycarbonyl; trimethylsilyl(fluorosulfonyl)difluoroacetate; unclassified drug; amination; Article; chemical bond; chemical reaction; chemical structure; column chromatography; cycloaddition