Oxalyl chloride → HCID 22905326, compound

Participants

Reaction Conditions

Reaction Steps

Oxalyl chloride (5.70 mL, 65.4 mmol) was added slowly to a rapidly stirred suspension of 14.6 g (48.9 mmol) of 5-(4-cyanobenzyloxy)-2-nitrobenzoic acid and 2 mL of dimethylformamide in 100 mL of benzene. When gas evolution ceased, the solution was heated briefly to 60° C., concentrated in vacuo, and redissolved in 75 mL of tetrahydrofuran. This solution was added dropwise to a rapidly stirred suspension of 8.50 g (55.3 mmol) of b-alanine ethyl ester hydrochloride and 21.1 g (251 mmol) of sodium bicarbonate in 325 mL of 2:1 tetrahydrofuran/water at 0° C. The mixture was warmed to ambient temperature for 12 h and the tetrahydrofuran was removed in vacuo. The residue was partitioned between ethyl acetate and 1N sodium bicarbonate and the aqueous phase was separated and extracted with ethyl acetate. The combined organics were washed with 1N sodium hydrogen sulfate, water, brine, dried over anhydrous magnesium sulfate, and concentrated to give 17.7 g (91%) of N-(5-(4-cyanobenzyloxy)-2-nitrobenzoyl)-b-alanine ethyl ester as a tan powder. 1H NMR (300 MHz, CDCl3) d 8.11 (1H, d, J=8.3 Hz, O--Ar--H), 7.71 (2H, d, J=8.3 Hz, NC--Ar--H2) d, J=8.3 Hz, NC--Ar--H2), 7.01 (2H, m, O--Ar--H2), 6.50 (1H, bt, J=5.9 Hz, N--H), 5.21 (2H, s, ArCH2O), 4.14 (2H, q, J=7.3 Hz, OCH2CH3), 3.69 (2H, bq, J=5.8 Hz, NCH2CH2), 2.70 (2H, t, J=5.8 Hz, NCH2CH2), 1.26 (3H, t, J=7.3 Hz, OCH2CH3); Exact mass (FAB, M+H+) calcd for C20H20N3O6 : 398.1352; Found: 398.1343.

Provenance & Evidence