A new synthesis of (-)-esermethole, based on the asymmetric alkylation at C(3) of racemic 1,3-dimethyl-5-methoxyoxindole (3), is described. The chloroacetyl derivatives of (-)-menthol and (S)-N-methyl-(1-phenylethyl) amine were chosen as chiral alkylating agents and used under different reaction conditions (temperature, solvent and base). In particular, the latter reacted with 3 in toluene at 10°C, in the presence of t-butyllitium, giving (3S,1′S)-N-methyl-N-(1′-phenylethyl)-1,3-dimethyl-5-methoxyoxindol-3-ilacetamide (10) with a 63% d.e.. This intermediate was easily separated from the undesired minor (3R,1′S) diastereomer (11) and converted to (-)-esermethole (99.6% e.e.) in two steps.

New asymmetric synthesis of (−)-esermethole / M. Pallavicini, E. Valoti, L. Villa, I. Resta. - In: TETRAHEDRON-ASYMMETRY. - ISSN 0957-4166. - 5:3(1994), pp. 363-370. [10.1016/S0957-4166(00)86207-2]

New asymmetric synthesis of (−)-esermethole

M. Pallavicini
Primo
;
E. Valoti
Secondo
;
1994

Abstract

A new synthesis of (-)-esermethole, based on the asymmetric alkylation at C(3) of racemic 1,3-dimethyl-5-methoxyoxindole (3), is described. The chloroacetyl derivatives of (-)-menthol and (S)-N-methyl-(1-phenylethyl) amine were chosen as chiral alkylating agents and used under different reaction conditions (temperature, solvent and base). In particular, the latter reacted with 3 in toluene at 10°C, in the presence of t-butyllitium, giving (3S,1′S)-N-methyl-N-(1′-phenylethyl)-1,3-dimethyl-5-methoxyoxindol-3-ilacetamide (10) with a 63% d.e.. This intermediate was easily separated from the undesired minor (3R,1′S) diastereomer (11) and converted to (-)-esermethole (99.6% e.e.) in two steps.
Settore CHIM/08 - Chimica Farmaceutica
Article (author)
File in questo prodotto:
Non ci sono file associati a questo prodotto.
Pubblicazioni consigliate

Caricamento pubblicazioni consigliate

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/180120
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 42
  • ???jsp.display-item.citation.isi??? 36
social impact