[(S)-1-(3-Bromo-2-cyclopropylamino-4-fluorophenylcarbamoyl)ethyl]carbamic acid tert-butyl ester → [(S)-1-(7-Bromo-1-cyclopropyl-6-fluoro-1H-benzoimidazol-2-yl)ethyl]carbamic acid tert-butyl ester

HRID 243140Notes

Reaction equation

[C:1]([O:5][C:6](=[O:25])[NH:7][C@H:8]([C:10](=O)[NH:11][C:12]1[CH:17]=[CH:16][C:15]([F:18])=[C:14]([Br:19])[C:13]=1[NH:20][CH:21]1[CH2:23][CH2:22]1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]>CC(O)=O>[C:1]([O:5][C:6](=[O:25])[NH:7][C@H:8]([C:10]1[N:20]([CH:21]2[CH2:23][CH2:22]2)[C:13]2[C:14]([Br:19])=[C:15]([F:18])[CH:16]=[CH:17][C:12]=2[N:11]=1)[CH3:9])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 70 °C

Procedure

[(S)-1-(3-Bromo-2-cyclopropylamino-4-fluoro-phenylcarbamoyl)ethyl]carbamic acid tert-butyl ester (1.05 g, 2.52 mmol) was taken up in AcOH (12 mL) and heated at 70° C. for 16 h. After cooling to RT, the volatiles were evaporated in vacuo and the residue was partitioned between EtOAc and a saturated solution of NaHCO3. The aqueous phase was further extracted with EtOAc and the combined organic fractions were washed with brine, dried (Na2SO4) and concentrated in vacuo. The resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane) to afford the title compound (771 mg, 77%) as a yellow oil. LCMS (Method C): RT 3.65 min [M+H]+ 398.09.

Workup

temperatureAfter cooling to RT
customthe volatiles were evaporated in vacuo
customthe residue was partitioned between EtOAc
extractionThe aqueous phase was further extracted with EtOAc
washthe combined organic fractions were washed with brine
dry with materialdried (Na2SO4)
concentrationconcentrated in vacuo
customThe resulting residue was purified by column chromatography (Si—PCC, gradient 0-50% EtOAc in cyclohexane)

Sources & evidence

ORD record: ord-e50e2a964d5b410c8134629c40b5d889
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653089B2

Reaction notes

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