Triethylamine → (S)-3-{3-[3-Ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-ureidomethyl}-piperidine-1-carboxylic Acid Tert-butyl Ester

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Reaction Steps

Racemic 3-hydroxymethylpiperidine-1-carboxylic acid tert-butyl ester was resolved using the procedure of B. Wirz and W. Walther, Tetrahedron Asymm. 1992, 3, 1049. The (R) isomer was converted into (S)-3-aminomethyl-piperidine-1-carboxylic acid tert-butyl ester by the method of K. Hilpert et al., J. Med. Chem. 1994, 37, 3889. A solution of this material (119 mg, 556 μmol) in N,N-dimethylformamide (4 mL) was treated with [3-ethyl-5-(1-methyl-1H-tetrazol-5-yl)-phenyl]-carbamic acid phenyl ester (180 mg, 556 μmol) and triethylamine (155 μL, 1.11 mmol) and the mixture was stirred at room temperature for 21 hours. The mixture was concentrated under vacuum, and the residue was dissolved in dichloromethane. The solution was washed with 1.0 N aqueous sodium hydroxide, dried over sodium sulfate and concentrated under vacuum. The residue was purified by flash chromatography, elution with 70% ethyl acetate in hexane, to provide a white glassy solid (193 mg, 78%). 1H NMR (300 MHz, CDCl3) δ7.64 (s, 1H), 7.55 (s, 1H), 7.18 (s, 1H), 4.20 (s, 3H), 3.9-3.6 (m, 3H), 3.28 (m, 1H), 3.05 (m, 2H), 1.83 (m, 1H), 2.66 (q, J=8 Hz, 2H), 1.9-1.5 (m, 5H), 1.46 (s, 9H), 1.24 (t, J=8 Hz, 3H).

Provenance & Evidence