O-Phenylenediamine → HCID 178451646, compound

Participants

Reaction Steps

2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (2926 mg, 7.71 mmol) was added to a solution of o-phenylenediamine, 4-chloro- (1000 mg, 7.01 mmol), 1-(tert-butoxycarbonyl)azetidine-3-carboxylic acid (1411 mg, 7.01 mmol), and triethylamine (1.075 mL, 7.71 mmol) in DMF (30 mL) under argon at 0° C. The mixture was stirred for 16 h with warming to RT before water (100 mL) was slowly added, at which time a suspension formed. The mixture was filtered and the collected solid was washed with water several times and then air-dried. The solid was dissolved in EtOAc and the mixture was washed with satd. NaHCO3, brine, dried (MgSO4), decolorized with activated charcoal, filtered, and concentrated in vacuo to give product as an off-white solid as a 4:1 ratio of regioisomers. A solution of tert-butyl 3-(2-amino-5-chlorophenylcarbamoyl)azetidine-1-carboxylate (2.28 g, 7.00 mmol) in acetic acid (20 mL) was heated to 100° C. for 1 h. The acetic acid was removed in vacuo and the resulting solid was partitioned between EtOAc and saturated NaHCO3. The layers were separated and the organic layer was dried (MgSO4), filtered, and concentrated in vacuo to give tert-butyl 3-(5-chloro-1H-benzo[d]imidazol-2-yl)azetidine-1-carboxylate as a light brown solid (2.03 g, 94%).

Provenance & Evidence