Compound 29
tert-Butyl ((cis-3-fluoro-1-(2,2,2-trifluoroacetyl)piperidin-2-yl)methyl)carbamate
From: The formation of all-cis-(multi)fluorinated piperidines by a dearomatization–hydrogenation process
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Compound data: 1H NMR
Compound data: 13C NMR
Compound data: 19F{1H} NMR
Compound data: Crystallographic data
Synthetic procedure: See article for the definitive version of this procedure and for full experimental details.
Compound 29 was prepared according to the general procedure outlined for compound 1 on 0.5 mmol scale, 3 mol% catalyst, 2 mmol HBpin, 1 M THF at 40 °C, purification with 0-30% EtOAc in pentane. The product was isolated as a colorless solid (39 mg, 0.12 mmol, 24%, d.r. 99:1). The reason for the low yielding transformation originates from the deprotection of the Boc-group during the addition of trifluoroacetic anhydride. The major diastereomer could be isolated by column chromatography. The product was present as a ~4:1 mixture of amide bond rotamers. Only the signals of the major rotamer are listed. Due to the broadening in NMR spectra we could not verify the orientation of the fluorine atom. However since we provided detailed NMR analysis on the simpler analogue (9), we therefore believe that the dominant orientation of the fluorine atom is equatorial. The equatorial orientation of the fluorine atom was confirmed by X-ray diffraction analysis. Single crystals of the title compound were obtained by crystallization at room temperature from a (1:1) mixture of n-hexane and ethyl acetate (slow evaporation of solvents). Detailed crystallographic data are reported in the corresponding section of the Supplementary Information. 1H NMR (400 MHz, CDCl3, 299 K) δ 4.96 (s, 1H), 4.77 – 4.52 (m, 2H), 3.97 – 3.85 (m, 1H), 3.73 (d, J = 13.0 Hz, 1H), 3.55 – 3.46 (m, 1H), 3.24 (d, J = 12.8 Hz, 1H), 2.15 – 1.99 (m, 1H), 1.94 – 1.77 (m, 2H), 1.64 – 1.50 (m, 1H), 1.38 (s, 9H); 13C NMR (101 MHz, CDCl3, 299 K) δ 157.34, 156.37, 116.53 (q, J = 287.7 Hz), 87.98 (d, J = 180.6 Hz), 79.96, 53.29 (d, J = 24.3 Hz), 40.43 (d, J = 3.5 Hz), 37.49, 35.25 (d, J = 3.7 Hz), 28.30, 23.24 (d, J = 9.9 Hz); 19F{1H} NMR (376 MHz, CDCl3, 299 K) δ -67.55 (minor rotamer), -68.91 (major rotamer), -181.06 (minor rotamer), -182.99 (major rotamer). ESI-MS: calculated [C13H20N2O3F4 +Na]+: 351.1302, found: 351.1304. IR ν = 3379.4 (m), 2970.4 (w), 2924.1 (w), 1705.1 (m), 1681.9 (s), 1527.6 (m), 1435.1 (w), 1365.6 (w), 1280.7 (m), 1249.9 (m), 1203.6 (s), 1141.9 (s), 1126.5 (s), 1041.6 (m), 1018.5 (m), 964.4 (m), 864.1 (m), 748.4 (m), 663.5 (m), 617.2 (m). M.p.: 88-89 °C.
