Diisopropylethylamine → (3R)-1-(2-Fluoro-4-nitrophenyl)pyrrolidin-3-ol

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Reaction Steps

(3R)-3-Hydroxypyrrolidine hydrochloride (20 g, 0.163 M) was suspended by stirring in acetonitrile (200 ml) under nitrogen at 50°, and treated with N,N-diisopropylethylarnine (52.5 g, 0.41 M) and 3,4-difluoronitrobenzene (25.9 g, 0.153 M). The mixture was heated at 90° for 17 hours, then the solvent evaporated. The residue was dissolved in dichloromethane (500 ml) and washed with 5% aqueous sodium dihydrogen phosphate (300 ml), which caused partial precipitation. The precipitate was filtered, washed, and the combined aqueous layers re-extracted with dichloromethane (200 ml). The organic layers were evaporated, and the residue combined with the previously filtered material, and dried by azeotroping with toluene to give the desired product (35 g), of sufficient quality for use without purification.

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