Water → (S)-ethyl 2-((3-bromo-2-nitrophenyl)amino)-propanoate

Participants

Reaction Steps

DIPEA (45.1 mL, 259 mmol) was added to a stirred solution of L-alanine ethyl ester hydrochloride (Aldrich; 34.1 g, 222 mmol) and 1-bromo-3-fluoro-2-nitrobenzene (126a; Ark Pharm, Inc., Libertyville, Ill.; 16.29 g, 74.0 mmol) in N,N-dimethylacetamide (15 mL) and the resulting yellow solution was stirred at RT for 15 min. A water-cooled reflux condenser was attached to the flask, and the resulting mixture was heated at 80° C. for 18 h. The reaction was cooled to RT, diluted with saturated aq. NH4Cl (100 mL), and extracted with EtOAc (4×75 mL). The combined organic extracts were dried over Na2SO4, filtered, and concentrated in vacuo to provide (S)-ethyl 2-((3-bromo-2-nitrophenyl)amino)propanoate (126b; 24.1 g) as a brown residue (contains 10% starting material by LCMS and 1H NMR), which was used directly in the subsequent step: 1H NMR (400 MHz, CDCl3) δ ppm 7.13 (1H, t, J=8.2 Hz), 7.00 (1H, d, J=8.0 Hz), 6.64 (1H, d, J=8.4 Hz), 5.89 (1H, d, J=6.8 Hz), 4.22 (2H, m, J=7.0, 7.0, 7.0 Hz), 4.14 (1H, quin, J=7.1 Hz), 1.51 (3H, d, J=7.0 Hz), 1.27 (3H, t, J=7.1 Hz). m/z (ESI, +ve) 317.0 (M+H)+.

Provenance & Evidence