Pyridine → (S)-tert-butyl 1-cyano-2-(3'-methylbiphenyl-4-yl)ethylcarbamate

Participants

Reaction Steps

To a solution of (S)-2-(tert-butoxycarbonylamino)-3-(3′-methylbiphenyl-4-yl)propanoic acid (1.37 g, 3.85 mmol) in THF (25 mL) were added ethyl chloroformate (0.407 mL, 4.24 mmol) and triethylamine (0.591 mL, 4.24 mmol) at room temperature. After being stirred for 0.5 hours, the resultant precipitate was removed by filtration. The filtrate was treated with ammonium hydroxide (10 mL) and stirred for 1.5 hours at room temperature. The reaction mixture was diluted with EtOAc and washed with H2O and brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The obtained residue was dissolved in THF (25 mL). TFAA (0.817 mL, 5.81 mmoL) and pyridine (0.935 mL, 11.56 mmol) were added at −10° C. and stirred for 2 hours. The reaction was quenched with saturated NaHCO3 aqueous solution. The mixture was extracted with EtOAc and washed with brine. The organic layer was dried over Na2SO4, concentrated under reduced pressure, and purified by silica gel flash column chromatography (EtOAc/heptane) to give (S)-tert-butyl 1-cyano-2-(3′-methylbiphenyl-4-yl)ethylcarbamate. 1H NMR (400 MHz, CDCl3) δ 1.45 (s, 9H), 2.42 (s, 3.04-3.19 (m, 2H), 4.68-4.94 (m, 2H), 7.17 (d, J=7.58 Hz, 1H), 7.31-7.41 (m, 5H), 7.59 (d, J=8.08 Hz, 2H); MS: m/z (MH+) 337; Retention time=1.60 min. (condition A).

Provenance & Evidence