反应详情

温度

60 °C

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), 7.52 (2H, 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, OCH2 CH3), 3.69 (2H, bq, J=5.8 Hz, NCH2CH2), 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.

1. concentrationconcentrated in vacuo
2. dissolutionredissolved in 75 mL of tetrahydrofuran
3. temperatureThe mixture was warmed to ambient temperature for 12 h
4. customthe tetrahydrofuran was removed in vacuo
5. customThe residue was partitioned between ethyl acetate and 1N sodium bicarbonate
6. customthe aqueous phase was separated
7. extractionextracted with ethyl acetate
8. washThe combined organics were washed with 1N sodium hydrogen sulfate, water, brine
9. dry with materialdried over anhydrous magnesium sulfate
10. concentrationconcentrated