Synthetic approaches to a chiral 4-amino-3-hydroxy piperidine with pharmaceutical relevance (original) (raw)
2012, Organic & Biomolecular Chemistry
Table of Contents I. General Experimental S1 II. Experimental and Spectral data S2 III. Microbial Assays S17 IV. Chromatograms S19 V. Copies of 1 H NMR and 13 C NMR Spectra S22 I. General Experimental All reaction were carried out under a nitrogen atmosphere with dry solvents and under anhydrous conditions unless otherwise noted. Reagents and solvents were purchased at the highest commercial quality and used without further purification, unless otherwise stated. Reactions were monitored by thin-layer chromatography (TLC) carried out on 0.25mm E. Merck silica gel plates (60F-254) using UV light as visualization agent and ethanolic solution of phosphomolybdic acid and cerium sulfate, and heat as developing agents. E. Merck silica gel (60, particle size, 0.040-0.063 mm) was used for flash column chromatography. NMR were recorded on a Bruker DRX-500 and calibrated using Electronic Supplementary Material (ESI) for Organic & Biomolecular Chemistry This journal is © The Royal Society of Chemistry 2012 S2 undeuterated solvent as an internal reference. Infrared (IR) spectra were recorded on a Perkin-Elmer 1600 series FT-IR spectrometer. High-resolution mass spectra (HRMS) were recorded on a Thermo Orbi-trap Discovery instrument. II. Experimental and Spectral data Preparation of sodium salt 7: Crude (3R,4R)-ethyl 1-benzyl-3-hydroxypiperidine-4carboxylate 5 (1.0 equiv, 9.27 g, 35.21 mmol; prepared from 9.2 g of ketoester 4) was placed in a 250 mL round bottom flask, followed by ethanol (97 mL). To the resulting dark solution, sodiumtrimethylsilanolate (1.65 equiv, 6.50 g, 57.94 mmol,) was added in one portion. The reaction was maintained at ambient temperature under nitrogen for 12 hours. The resulting solids were collected by filtration using a Buchner funnel. The crude product was rinsed with two 10 mL portion of ethanol followed to 10 mL of MTBE. The resulting material was dried under vacuum for 4 hours to yield 7 (7.79 g, 30.28 mmol, 86%) as an off-white solid.
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The stratagem for literature searching in organic and inorganic synthesis increasingly becomes easier with the computer database. However, the dilemma has now become how to select one procedure instead of other. For neophyte, this is a difficult task, deciding the reaction conditions to be carried out to have the best chance of success. This practical procedure collection intended to serve lab-mate by sharing author’s own experience through most commonly used experimental procedures from established groups, reviewed journals and/or patents. Under the title of each experimental procedure, brief commentaries are often offered which summarize the authors’ personal experience. For the final products, detailed spectral data are not given because they simply take up too much space. We had a good time putting together these experimental procedures. We have even been using the manuscript ourselves quite often. Hopefully, you will find it as useful. We welcome your critique.
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