ethyl 3-(2-amino-3-fluoroanilino)propanoate

Conditions: temp:80.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A disposable tube was charged with ethyl 3-(2-amino-3-fluorophenylamino)propanoate (800 mg, 3.54 mmol) and a stirbar. Toluene (10 mL) was added, followed by tetraisopropoxytitanium (523 μl, 1.768 mmol), and the solution was stirred at 80° C. 0.5 h. The solution was diluted with ethyl acetate, concentrated with celite, and purified by silica gel chromatography (eluting with hexanes/ethyl acetate) to yield 9-fluoro-4,5-dihydro-1H-benzo[b][1,4]diazepin-2(3H)-one as a white amorphous solid (0.618 g, 3.43 mmol, 97%). 0.5 h concentrated with celite purified by silica gel chromatography (eluting with hexanes/ethyl acetate)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A round bottomed flask was charged with palladium on carbon (0.306 g, 0.287 mmol) and a stirbar. Ethyl 3-(3-fluoro-2-nitrophenylamino)propionate (1.473 g, 5.75 mmol) in 1:1 EtOH:EtOAc (40 mL) was added, and the flask was evacuated and purged with hydrogen three times before being stirred at room temperature overnight. The mixture was filtered, concentrated with celite, and purified by silica gel chromatography (eluting with hexanes/ethyl acetate) to yield ethyl 3-(2-amino-3-fluorophenylamino)propanoate as a brown oil (1.074 g, 4.75 mmol, 83%). the flask was evacuated purged with hydrogen three times The mixture was filtered concentrated with celite purified by silica gel chromatography (eluting with hexanes/ethyl acetate)