Synthesis of trans-4-Triazolyl-Substituted 3-Hydroxypiperidines

Abstract

The synthesis of tert-butyl trans-4-ethynyl-3-hydroxypiperidine-1-carboxylate is described via regioselective ring-opening of a racemic N-Boc-protected 7-oxa-3-azabicyclo[4.1.0]heptane, and serves as a new scaffold for the preparation of substituted piperidines. The terminal alkyne is converted into 1,4- and 1,5-disubstituted 1,2,3-triazoles through 1,3-dipolar cycloaddition reactions with organic azides.

Key words

piperidine - epoxide - alkyne - azide - triazole

References

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12

Crystal data for compound 3: C₁₅H₂₇NO₃Si, MW = 297.47, triclinic, a = 5.7413(15), b = 11.872(3), c = 14.437(5) Å, α = 112.127(15), β = 97.874(14), γ = 98.495(10), V = 881.4(4) Å^³, d _(calcd) = 1.121 g cm^-³, T = 123(2) K, space group P-1, Z = 2. Data collected, 15714, R _(int) 0.0185. The structure was solved by direct methods, and least-squares refinement of the model based on 5471 independent data [4982 reflections with I>2σ(I)] converged to a final R1 = 0.0321 and wR2 = 0.0885, respectively, S = 1.067. Selected geometric parameters (Å, ˚); N1-C1 1.4562(10), N1-C5 1.4646(10), N1-C11 1.3505(10), C1-C2 1.5242(11), C2-O2 1.4201(10), C2-C3 1.5432(11), C3-C4 1.5370(12), C3-C6 1.4706(12), C4-C5 1.5247(12), C6-C7 1.2068(13), C7-Si1 1.8339(11), C11-O2 1.2254(10), C11-O3 1.3441(10), O3-C12 1.4675(10), C11-N1-C1 118.77(7), C11-N1-C5 123.83(7), C1-N1-C5 114.35(6), N1-C1-C2 110.96(6), O1-C2-C1 111.74(6), O1-C2-C3 107.16(6), C1-C2-C3 111.00(6), C11-O3-C12 120.39(7), C6-C3-C4 112.00(7), C6-C3-C2 109.45(7), C4-C3-C2 109.88(6), C5-C4-C3 111.30(6), N1-C5-C4 109.66(6), C7-C6-C3 176.62(9), C6-C7-Si1 172.82(8), O2-C11-O3 123.90(7), O2-C11-N1 124.53(7), O3-C11-N1 111.54(7). CCDC 793221 contains the supplementary crystallographic data for 3. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/data_request/cif.