Ethyl 1-((2-amino-5-bromophenylamino)methyl)cyclopropanecarboxylate → 7-bromo-4,5-dihydrospiro[benzo[b][1,4]diazepine-3,1'-cyclopropan]-2(1H)-one
Reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][C:3]=1[NH:9][CH2:10][C:11]1([C:14]([O:16]CC)=O)[CH2:13][CH2:12]1>C1(C)C=CC=CC=1.O.C(O[Ti](OC(C)C)(OC(C)C)OC(C)C)(C)C>[Br:8][C:5]1[CH:6]=[CH:7][C:2]2[NH:1][C:14](=[O:16])[C:11]3([CH2:10][NH:9][C:3]=2[CH:4]=1)[CH2:13][CH2:12]3Participants
5
Reactant 1
Product 1
Reagents, catalysts & solvents 3
Conditions
- Temperature
- 90 °C
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.
Workup
- additionAfter addition
- extractionextracted with ethyl acetate (200 mL)
- customThe organic layer was separated
- dry with materialdried by sodium sulfate
- filtrationfiltered
- concentrationconcentrated
Sources & evidence
- ORD record
- ord-626baeeebd6a4ee3b16942135ca96fff
- Source dataset
- uspto-grants-2016_08
- Patent number
- US09422292B2
Reaction notes
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