Triphenylphosphine → (2R,4S)-5-Biphenyl-4-yl-4-{3-[1-(2-cyano-ethyl)-1H-tetrazol-5-yl]-propionylamino}-2-methyl-pentanoic acid ethyl ester

Participants

Reaction Steps

To a solution of (2R,4S)-5-biphenyl-4-yl-4-[3-(2-cyano-ethylcarbamoyl)-propionylamino]-2-methyl pentanoic acid ethyl ester (150 mg, 0.324 mmol) in THF (2 mL) is added triphenylphosphine (85 mg, 0.324 mmol). After stirring for 10 minutes, diisopropyl azodicarboxylate (0.063 mL, 0.324 mmol) and trimethylsilyl azide (0.043 mL, 0.324 mmol) are added. The mixture is stirred for 8 hours and additional triphenylphosphine, diisopropyl azocarboxylate, and trimethylsilyl azide (each 0.324 mmol) are added. After stirring overnight, the mixture is concentrated and purified by silica gel column chromatography to give (2R,4S)-5-biphenyl-4-yl-4-{3-[1-(2-cyano-ethyl)-1H-tetrazol-5-yl]-propionylamino}-2-methyl-pentanoic acid ethyl ester. HPLC Retention time 1.42 minutes (condition B); MS 489 (M+1); 1H NMR (400 MHz, CDCl3) δ ppm 1.11 (d, J=7.07Hz, 3H), 1.23 (t, J=7.07Hz, 3H), 1.47 (ddd, J=4.29, 10.10, 14.39Hz, 1H), 1.91 (ddd, J=4.04, 9.60, 13.64Hz, 1H), 2.31-2.41 (m, 1H), 2.67-2.81 (m, 4H), 3.00 (t, J=6.82Hz, 2H), 3.05-3.17 (m, 2H), 4.03-4.22 (m, 3H), 4.50-4.68 (m, 2H), 5.69 (d, J=9.09Hz, 1H), 7.14 (d, J=8.08Hz, 2H), 7.34 (t, J=7.33Hz, 1H), 7.44 (t, J=7.83Hz, 2H), 7.50 (d, J=8.34Hz, 2H), 7.59 (d, J=7.07Hz, 2H).

Provenance & Evidence