[1-(2-Phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester → 1-(1-Phenyl-1H-benzoimidazol-2-yl)ethylamine

HRID 242779Notes

Reaction equation

C(OC(=O)[NH:7][CH:8]([C:10](=O)[NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=1[NH:18][C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1)[CH3:9])(C)(C)C>CC(O)=O.C1(C)C=CC=CC=1>[C:19]1([N:18]2[C:13]3[CH:14]=[CH:15][CH:16]=[CH:17][C:12]=3[N:11]=[C:10]2[CH:8]([NH2:7])[CH3:9])[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

Conditions

Temperature: 80 °C

Procedure

[1-(2-Phenylaminophenylcarbamoyl)ethyl]carbamic acid tertbutyl ester (400 mg, 1.59 mmol) was suspended in AcOH (4 mL) and the resulting mixture was heated at 80° C. for 12 h whereupon the mixture clarified. The cooled solution was diluted with toluene and volatiles removed under reduced pressure. The resulting residue was stirred with TFA (4 mL) for 2 h and the resulting solution was loaded onto an SCX-2 cartridge which was initially washed with MeOH. The product was eluted with 2M NH3/MeOH and further purified by column chromatography (Si—PCC, gradient 0-6% MeOH in DCM) affording 1-(1-phenyl-1H-benzo[d]imidazol-2-yl)ethanamine as a white crystalline solid (211 mg, 80%). LCMS: RT 0.27 min [M−NH2]+ 221.1. The enantiomers, (S)-1-(1-phenyl-1H-benzo[d]imidazol-2-yl)ethanamine and (R)-1-(1-phenyl-1H-benzo[d]imidazol-2-yl)ethanamine can be resolved and separated. Alternatively, (S)-1-(1-phenyl-1H-benzo[d]imidazol-2-yl)ethanamine can be prepared from enantiopure (S)-2-tertbutoxycarbonylaminopropionic acid.

Workup

customremoved under reduced pressure
washwas initially washed with MeOH
washThe product was eluted with 2M NH3/MeOH
customfurther purified by column chromatography (Si—PCC, gradient 0-6% MeOH in DCM)

Sources & evidence

ORD record: ord-4999cf02e00b4fa2a7c1f9dbaa9a3de1
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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