Mechanistic investigation on 2-aza-spiro[4,5]decan-3-one formation from 1-(aminomethyl)cyclohexylacetic acid (gabapentin)

Tetrahedron

Volumn 64, Issue 28, 2008, Pages 6739-6743

  Zambon, Elena ^a   Giovanetti, Roberto ^b   Cotarca, Livius ^b   Pasquato, Lucia ^a  

^a UNIVERSITY OF TRIESTE   (Italy)

^b ZaCh System SpA   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 AZA SPIRO[4,5]DECAN 3 ONE; GABAPENTIN;

ACID BASE BALANCE; ARTICLE; CATALYSIS; CYCLIZATION; DRUG SCREENING; FLUOROMETRY; IONIC STRENGTH; PH; POTENTIOMETRY; PRIORITY JOURNAL; PROTON NUCLEAR MAGNETIC RESONANCE;

EID: 45449095457     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tet.2008.05.010     Document Type: Article

References (21)

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12. HPLC cannot be used to monitor the cyclization reaction since in the kinetic conditions the gabapentin alone shows more than one peak. Moreover, during the reaction, there are at least two peaks that increase. As shown by the NMR experiments this behavior is not due to the presence or formation of impurities but it is probably associated to the use of the buffer. Indeed, in the absence of buffer the HPLC of gabapentin and of the cyclic lactam gives only one peak, as expected. For these analysis we explored several stationary phases, we analyzed different buffering solutions but, also using the same conditions reported in Ref. 9, we always experienced the same reproducible problems.
13. This pH value, that corresponds to the calculated minimum pseudo-first order rate constant, has been obtained by interpolation of the curve of Figure 1.
14. Preliminary DOSY NMR experiments show that at concentration above 0.1 M gabapentin forms small aggregates.
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