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. 2010 Jul 12;12(4):566-70.
doi: 10.1021/cc100054u.

Solid-phase synthesis of N-substituted pyrrolidinone-tethered N-substituted piperidines via Ugi reaction

Zhang Liu  1 , Adel Nefzi
Affiliations

Solid-phase synthesis of N-substituted pyrrolidinone-tethered N-substituted piperidines via Ugi reaction

Zhang Liu et al. J Comb Chem. .

Abstract

Starting with resin-bound glutamic acid, an efficient synthesis of N-substituted pyrrolidinones is described, using the Ugi four-component reaction (U-4CR). The same methodology is employed to produce N-substituted pyrrolidinone tethered N-substituted piperidines.

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Figures

Scheme 1
Scheme 1
Reagents and conditions: (a) 55% TFA/DCM, 1h; (b) 20% piperidine/DMF, 10 min, twice; (c) Benzyl isocyanide/Cyclohexanone (1:1) in Acetonitrile/MeOH (4:1); (d) HF/anisole, 1.5 h, 0 °C.
Scheme 2
Scheme 2
Reagents and conditions: (a) Benzyl isocyanide, N-Boc-4-piperidinone, acetonitrile/methanol (4:1), 65 °C, 24 h; (b) 55% TFA/DCM; (c) Acid, DIC, HOBt, DMF, r.t., overnight or Sulfonyl chloride/isocyanate/thioisocyanate, DIEA, DMF, r.t., overnight; (d) HF cleavage, 0 °C, 1.5 h.
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