A practical synthesis of differentially protected 2-(Hydroxymethyl) piperazines

Article abstract of DOI:10.1021/jo701465h

(Chemical Equation Presented) An efficient and scalable synthesis of three differentially protected 2-(hydroxymefhyl)piperazines is presented, starting from optically active and commercially available (2S)-piperazine-2-carboxylic acid dihydrochloride. These synthetic building blocks are useful in the preparation of biologically active compounds and as chemical scaffolds for the construction of combinatorial libraries.

Full text of DOI:10.1021/jo701465h

Supplementary materials for the manuscript “A Practical Synthesis of Differentially-
Protected 2-(Hydroxymethyl)piperazines” Hongwu Gao and Adam R. Renslo
Contents:
Page S2: General Methods
Page S3: Representative 1H NMR spectrum (300 MHz, CDCl3) of compound 6 as
obtained using the experimental procedures described in manuscript.
Page S4: Representative 1H NMR spectrum (300 MHz, CDCl3) of compound 2 as
obtained using the experimental procedures described in manuscript.
Page S5: Representative 1H NMR spectrum (300 MHz, DMSO-d6) of compound 3 as
obtained using the experimental procedures described in manuscript.
S1

General Methods
1H NMR and 13C NMR spectra were recorded at 300 MHz and 75 MHz, respectively.
Chemical shifts are reported in δ units (ppm) relative to tetramethylsilane as an internal
standard. Splitting paterns are reported as follows: (s = singlet, bs = broad singlet, br =
broad, d = doublet, t = triplet, q = quartet, m = multiplet). Coupling constants (J) are
reported in hertz (Hz). All reagents and solvents were purchased from commercial
suppliers and used as received unless otherwise indicated. Solvent removal was
accomplished with a rotary evaporator at ca 10-50 Torr. Column chromatography was
performed using silica gel (230-400 mesh) and ethyl acetate/hexane as eluent.
S2

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S5