A practical synthesis of (3R,4R)-N-tert-butoxycarbonyl-4-hydroxymethylpyrrolidin-3-ol?

Organic & Biomolecular Chemistry Pub Date: 2007-07-20 DOI: 10.1039/B708796A

Abstract

The title compound (+)-5, required for production of transition state analogue inhibitors of enzymes involved in T-cell-dependent disorders, was synthesized in five steps. A 1,3-dipolar cycloaddition of the nitrone formed from formaldehyde and N-benzylhydroxylamine to diethyl maleate gave the racemic cis-isoxazolidine (±)-7. Reduction of the N–O bond of this compound gave pyrrolidone (±)-8 in excellent yield. A very efficient enzymic resolution of this racemic product led to the title enantiomer (+)-5. This route employs only one chromatographic purification.

Graphical abstract: A practical synthesis of (3R,4R)-N-tert-butoxycarbonyl-4-hydroxymethylpyrrolidin-3-ol
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