Hydrochloric Acid → [5-Fluoro-2-(3-nitro-benzylcarbamoyl)-phenoxy]-acetic acid ethyl ester

Participants

Reaction Conditions

Reaction Steps

A solution of 4-fluoro-2-hydroxy-N-(3-nitro-benzyl)-benzamide (5.00 g, 17.2 mmol) in acetone (86.0 mL) was treated with aq 2 N K2CO3 (13.0 mL, 25.8 mmol) and ethyl bromoacetate (1.50 mL, 9.66 mmol) and heated to 50° C. for 2 h. The solution was cooled to 0° C. and acidified to pH of 1 with 2 N HCl. The solution was diluted with ethyl acetate and washed with saturated aq NaCl. The organic layer was dried over MgSO4, filtered and concentrated. Purification by MPLC(10-100% ethyl acetate in heptane, 23 mL/min, 75 min) to give [5-fluoro-2-(3-nitro-benzylcarbamoyl)-phenoxy]-acetic acid ethyl ester as a pale yellow solid (6 g, 93%): mp 78-80° C.; Rf 0.26 (40% ethyl acetate in heptane); 1H NMR (DMSO-d6 300 MHz) δ 9.01 (t, J=6 Hz, 1H), 8.19 (t, J=1.8 Hz, 1H), 8.10 (dd, J1=8.1 Hz, J2=1.5 Hz, 1H), 7.89 (dd, J1=8.7 Hz, J2=6.9 Hz, 1H),7.79 (d, J=7.5 Hz, 1H), 7.61 (t, J=8.1 Hz, 1H), 7.11 (dd, J1=11.1 Hz, J2=2.4 Hz, 1H), 6.92 (dt, J1=8.4 Hz, J2=2.4 Hz, 1H), 5.0 (s, 2H), 4.63 (d, J=6.3 Hz, 2H), 4.15 (q, J=7.2 Hz, 2H) 1.17 (t, J=6.5 Hz, 3H). ESI-LC/MS m/z calcd for C18H17FN2O6: 376.4. Found 377.0 (M+1)+. Anal. calcd for C18H17FN2O6: C, 57.45; H, 4.55; N, 7.44. Found : C, 57.47; H, 4.64; N, 7.28.

Provenance & Evidence