Synthesis 2005(19): 3456-3462  
DOI: 10.1055/s-2005-918462
PAPER
© Georg Thieme Verlag Stuttgart · New York

Gram-Scale Synthesis of N-Aryl- and N-Aryl-N′-methylpiperazines on a Novel­, Water-Swellable, Oxethane-Linked Poly(ethylene glycol) High-Loading Resin

Hans Christian Rudbecka, Ib Johannsenb, Ole Nielsena, Thomas Ruhlanda, Michael Bech Sommera, David Tannerc, Robert Dancer*a
a H. Lundbeck A/S, Ottiliavej 7-9, 2500 Valby, Denmark
Fax: +4536438256; e-Mail: rda@lundbeck.com;
b VersaMatrix A/S, Gamle Carlsbergvej 10, 2500 Valby, Denmark
c Department of Chemistry, Technical University of Denmark, Building 201, Kemitorvet, 2800 Kongens Lyngby, Denmark
Further Information

Publication History

Received 16 September 2005
Publication Date:
14 November 2005 (online)

Abstract

A new methodology for the synthesis of N-arylpiperazines was developed using a poly(ethylene glycol)-derived solid support. The reactions proceeded in up to 60% overall yield over four steps. The scope and limitations of the method are discussed, as well as the utility of 13C gel-phase NMR spectroscopy for reaction monitoring.

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2

Price for 100 g of Versabeads™ VO400 loading 2 mol·kg-1 (as used in this article): e 739 equal to e 370 per mol. Price for 100 g of Rapp Polymere hydroxymethyl polystyrene loading 1.5 mol·kg-1: e 360 equal to e 240 per mol (price for 100 g of Rapp Polymere TentaGel Standard (water compatible), loading 0.3 mol·kg-1: e 1010 equal to e 33667 per mol)

16

Compound 3h was only sparingly soluble in the NMR solvent, so quaternary carbon peaks were not visible.

17

Gentle magnetic stirring did not appear to damage the resin. Vigorous magnetic stirring, however, caused significant damage due to grinding.