Cesium carbonate → 1-Azetidinecarboxylic acid, 3-(6-bromo-2-methyl-1H-benzimidazol-1-yl)-, 1,1-dimethylethyl ester

HRID 879533Notes

Reaction equation

HRID 879533 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([N+:8]([O-])=O)=[C:4](F)[CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].[NH2:18][CH:19]1[CH2:22][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:20]1.[CH3:30][C:31](OCC)(OCC)OCC>CN(C=O)C.CCOC(C)=O.O.CCO.CCOC(C)=O.CC(O)=O.[Pt]>[Br:1][C:2]1[CH:7]=[CH:6][C:5]2[N:8]=[C:30]([CH3:31])[N:18]([CH:19]3[CH2:20][N:21]([C:23]([O:25][C:26]([CH3:29])([CH3:28])[CH3:27])=[O:24])[CH2:22]3)[C:4]=2[CH:3]=1

Participants

11

Reactant 4

HCID 10796Cesium carbonateHCID 66221Triethyl orthoacetateHCID 1516507Tert-butyl 3-aminoazetidine-1-carboxylateHCID 27833624-Bromo-2-fluoro-1-nitrobenzene

Product 1

HCID 867003531-Azetidinecarboxylic acid, 3-(6-bromo-2-methyl-1H-benzimidazol-1-yl)-, 1,1-dimethylethyl ester

Reagents, catalysts & solvents 6

HCID 23939PlatinumCatalystHCID 176Acetic AcidSolventHCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolventHCID 21584252Ethanol ethylacetateSolvent

Procedure

A flask was charged with 4-bromo-2-fluoro-1-nitrobenzene (529 mg, 2.41 mmol), Cs2CO3 (2.45 g, 7.52 mmol), and diluted with DMF (6 mL). To this was added tert-butyl 3-aminoazetidine-1-carboxylate (0.75 mL, 4.78 mmol) at room temperature and the reaction mixture was allowed to stir for 16 hours. The mixture was diluted with EtOAc and H2O and the layers were separated. The aqueous layer was extracted with EtOAc and the combined organic extracts were dried over Na2SO4, filtered through a small pad of silica gel eluting with 30% EtOAc/Hex, and concentrated in vacuo to afford a crude residue. The flask containing the crude residue was charged 5 wt % Pt/C (140 mg) and then diluted with 2:1 EtOH/EtOAc (30 mL). The flask was evacuated then backfilled with H2 (3 cycles) and stirred under a hydrogen atmosphere for 20 minutes, at which time, the flask was purged with N2, filtered through a pad of Celite, and concentrated in vacuo to provide a crude residue. The crude residue was taken up in AcOH (10 mL) and MeC(OEt)3 (1 mL) was added at room temperature, stirred for 15 minutes, and then the solution was concentrated in vacuo. The crude residue was purified by silica gel column chromatography (30-70% EtOAc/Hex gradient) to afford the desired product. LCMS-ESI+: calc'd C16H21BrN3O2: 366.1 (M+H+); Found: 366.1 (M+H+).

Workup

  1. customthe layers were separated
  2. extractionThe aqueous layer was extracted with EtOAc
  3. dry with materialthe combined organic extracts were dried over Na2SO4
  4. filtrationfiltered through a small pad of silica gel eluting with 30% EtOAc/Hex
  5. concentrationconcentrated in vacuo
  6. customto afford a crude residue
  7. customThe flask was evacuated
  8. stirringstirred under a hydrogen atmosphere for 20 minutes, at which time
  9. customthe flask was purged with N2
  10. filtrationfiltered through a pad of Celite
  11. concentrationconcentrated in vacuo
  12. customto provide a crude residue
  13. stirringstirred for 15 minutes
  14. concentrationthe solution was concentrated in vacuo
  15. customThe crude residue was purified by silica gel column chromatography (30-70% EtOAc/Hex gradient)

Sources & evidence

ORD record
ord-a30cbefc534d41a886c54859485d089f
Source dataset
uspto-grants-2015_03
Patent number
US08987250B2

Reaction notes

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