ethyl 1-[(2-amino-5-bromoanilino)methyl]cyclopropane-1-carboxylate

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of ethyl 1-((2-amino-5-bromophenylamino)methyl)cyclopropanecarboxylate (624 mg, 2.0 mmol) in toluene (15 mL) was added dropwise tetraisopropoxytitanium (1.2 g, 4.0 mmol). After addition was complete, the reaction was stirred for 12 hours at 90° C. The mixture was diluted with water (200 mL), extracted with ethyl acetate (200 mL). The organic layer was separated, dried by sodium sulfate, filtered and concentrated to give the crude 7-bromo-4,5-dihydrospiro[benzo[b][1,4]diazepine-3,1′-cyclopropan]-2(1H)-one (400 mg, 75%) as white solid, used for the next step without further purification. After addition extracted with ethyl acetate (200 mL) The organic layer was separated dried by sodium sulfate filtered concentrated

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Iron powder (448 mg, 8.0 mmol) was added to a mixture of ethyl 1-((5-bromo-2-nitrophenylamino)methyl)cyclopropanecarboxylate (684 mg, 2.0 mmol), ammonium chloride aqueous (6 mL) and ethanol (20 mL). The reaction was heated to 70° C. and maintained at the 70° C. for 2 hours. The mixture solution was filtered. The filtrate was evaporated, diluted with water (100 mL), extracted with ethyl acetate (100 mL), and dried by sodium sulfate. The mixture was filtered. The filtrate was concentrated and purified by column chromatography (silica gel, petroleum ether/ethyl acetate=5:1) to give ethyl 1-((2-amino-5-bromophenylamino)methyl)cyclopropanecarboxylate (474 mg, 76%) as off-white solid. maintained at the 70° C. for 2 hours The mixture solution was filtered The filtrate was evaporated diluted with water (100 mL) extracted with ethyl acetate (100 mL) dried by sodium sulfate The mixture was filtered The filtrate was concentrated purified by column chromatography (silica gel, petroleum ether/ethyl acetate=5:1)