Triphenylphosphine → (1S)-3-[5-(1-Amino-2-biphenyl-4-yl-ethyl)-tetrazol-1-yl]-propionitrile

Participants

Reaction Steps

To a solution of (S)-tert-butyl 3-(biphenyl-4-yl)-1-(2-cyanoethylamino)-1-oxopropan-2-ylcarbamate (563 mg, 1.431 mmol) and triphenylphosphine (450 mg, 1.717 mmol) in THF (10 mL) were added DIAD (0.334 mL, 1.717 mmol) and TMSN3 (0.228 mL, 1.717 mmol) at room temperature. After 2 hours, additional triphenylphosphine (180 mg, 0.687 mmol), DIAD (0.134 mL, 0.687 mmol) and TMSN3 (0.0912 mL, 0.687 mmol) were added. After being stirred overnight, additional triphenylphosphine (180 mg, 0.687 mmol), DIAD (0.134 mL, 0.687 mmol) and TMSN3 (0.0912 mL, 0.687 mmol) were added. After being additional 3 hours, the reaction mixture was concentrated and purified by silica gel flash column chromatography (eluent; EtOAc/heptane). The obtained product was treated with 4M HCl in dioxane (10 mL) at room temperature. After being stirred for 1 hour, the reaction mixture was concentrated. The residue was diluted with EtOAc, washed with saturated NaHCO3aq and brine. The organic layer was dried over Na2SO4, concentrated and purified by silica gel flash column chromatography (eluent; MeOH/DCM) to give (S)-3-(5-(1-amino-2-(biphenyl-4-yl)ethyl)-1H-tetrazol-1-yl)propanenitrile (334 mg). 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 2.83 (dt, J=6.82, 16.9 Hz, 1H), 2.96 (dt, J=6.82, 13.89 Hz, 1H), 3.21 (dd, J=8.08, 13.64 Hz, 1H), 3.42 (dd, J=6.06, 13.64 Hz, 1H), 4.47-4.59 (m, 2H), 4.60-4.68 (m, 1H), 7.21 (d, J=8.08 Hz, 2H), 7.33-7.39 (m, 1H), 7.42-7.48 (bt, 2H), 7.54-7.60 (m, 3H).

Provenance & Evidence