Hydroxylamine → 2-[5-(4-Chloro-2-cyano-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1185840Notes

Reaction equation

HRID 1185840 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[CH:25]=O)=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].NO.CC([Si](Cl)(C)C)(C)C.[NH:37]1C=CN=C1>C(O)C.CCOC(C)=O.CN(C=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:10][CH:9]1[C:13]1[NH:14][C:15]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][C:19]=2[C:25]#[N:37])=[CH:16][N:17]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 4

HCID 787HydroxylamineHCID 795Imidazole2×HCID 28928tert-Butyldimethylsilyl chloride2×HCID 723382662-[5-(4-Chloro-2-formyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666205872-[5-(4-Chloro-2-cyano-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl esterYield 51.2%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

2-[5-(4-Chloro-2-formyl-phenyl)-1H-imidazol-2-yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (985 mg, 2.62 mmol) was dissolved in ethanol (20 mL) and hydroxylamine (50% w/w in H2O, 642 μL, 10.48 mmol) was added. After stirring at room temperature for 15 h, the solution was concentrated. To the crude oxime was added TBSCl (474 mg, 3.14 mmol), imidazole (357 mg, 5.24 mmol) and DMF (10 mL). The reaction mixture was stirred at 120° C. for 80 minutes at which point more TBSCl (237 mg, 1.58 mmol) and imidazole (177 mg, 2.60 mmol) were added. The reaction mixture was stirred an additional 17 hours at 120° C. then cooled to room temperature, diluted with EtOAc. The organic phase was washed with saturated aqueous NaHCO3 and brine then dried over MgSO4, filtered and concentrated under reduced pressure. The crude residue was purified by silica column chromatography (25% to 50% EtOAc/Hexane) to afford the title compound 2-[5-(4-Chloro-2-cyano-phenyl)-1H-imidazol-2-Yl]-pyrrolidine-1-carboxylic acid tert-butyl ester (500 mg, 51%).

Workup

  1. concentrationthe solution was concentrated
  2. additionwere added
  3. stirringThe reaction mixture was stirred an additional 17 hours at 120° C.
  4. temperaturethen cooled to room temperature
  5. washThe organic phase was washed with saturated aqueous NaHCO3 and brine
  6. dry with materialthen dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated under reduced pressure
  9. customThe crude residue was purified by silica column chromatography (25% to 50% EtOAc/Hexane)

Sources & evidence

ORD record
ord-7a0aeb3bbae14f5b8f43c0496c800e3d
Source dataset
uspto-grants-2014_03
Patent number
US08669234B2

Reaction notes

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