O-Phenylenediamine → HCID 178451646, compound

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%).

1. additionwas slowly added, at which time a suspension
2. customformed
3. filtrationThe mixture was filtered
4. washthe collected solid was washed with water several times
5. customair-dried
6. dissolutionThe solid was dissolved in EtOAc
7. washthe mixture was washed with satd
8. dry with materialNaHCO3, brine, dried (MgSO4)
9. filtrationfiltered
10. concentrationconcentrated in vacuo
11. customto give product as an off-white solid as a 4:1 ratio of regioisomers
12. customThe acetic acid was removed in vacuo
13. customthe resulting solid was partitioned between EtOAc and saturated NaHCO3
14. customThe layers were separated
15. dry with materialthe organic layer was dried (MgSO4)
16. filtrationfiltered
17. concentrationconcentrated in vacuo

ORD record

ord-8ea0b76994b042ffac8f723bd6efc211

Source dataset

uspto-grants-2015_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08946230B2