One-pot multistep synthesis of 3-aminoindolizine derivatives

Tetrahedron Letters

Volumn 52, Issue 12, 2011, Pages 1392-1394

  Li, Lianhai ^a,b   Chua, Waepril Kimberly S ^a  

^a MERCK FROSST CENTRE FOR THERAPEUTIC RESEARCH   (Canada)

^b NONE   (Canada)

Author keywords

Indolizine; Multistep; One pot; Synthesis

Indexed keywords

3 AMINOINDOLIZINE DERIVATIVE; ESTER; HANTZSCH ESTER; INDOLIZINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; CHEMICAL REACTION; ONE POT SYNTHESIS;

EID: 79951775173     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tetlet.2011.01.087     Document Type: Article

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18. At the end of our study, we re-examined more closely the formation of 1e from 2a and 3e (Table 1, entry 9). We found that under the original reaction conditions as described in Table 1, entry 9, an enamine 11 side product was formed (Fig. A) in ca. 20% yield. Compound 11 is stable to flash chromatography over silica gel column (Chemical Equation Presented) We then found that without the use of Knoevenagel condensation catalyst piperidinium acetate, the formation of 11 was reduced but the reaction yield of 1e was hardly effected (46% without vs 44% with piperidinium acetate). In order to further suppress the formation of 11, we used 1.4 instead of 1.0 equiv of 3e in the absence of a catalyst, and found that the yield of 1e was improved from 46% to 59% (Scheme A).
19. Attempts to cyclize 8a under a variety of conditions failed to provide any cyclized product. Further exploration needs to be done.