Ammonium Acetate → 6-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester

HRID 79820Notes

Reaction equation

HRID 79820 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH:14]([C:15](=O)[NH:16][CH2:17][C:18]([C:20]2[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][CH:21]=2)=O)[CH2:13][C:10]2([CH2:12][CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C([O-])(=O)C.[NH4+:32]>CCOC(C)=O>[C:1]([O:5][C:6]([N:8]1[CH:14]([C:15]2[NH:32][C:18]([C:20]3[CH:25]=[CH:24][C:23]([Br:26])=[CH:22][CH:21]=3)=[CH:17][N:16]=2)[CH2:13][C:10]2([CH2:12][CH2:11]2)[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

4

Reactant 2

HCID 517165Ammonium AcetateHCID 666202116-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester

Product 1

HCID 666203726-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl esterYield 61.4%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
140 °C

Procedure

15 mL Xylenes was added to 6-[2-(4-Bromo-phenyl)-2-oxo-ethylcarbamoyl]-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester (424 mg, 0.97 mmol) and ammonium acetate (20 eq., 1.5 g). The mixture was heated in microwave at 140° C. for 60 minutes. The mixture was diluted with EtOAc and washed with sat.NaHCO3 aqueous solution. The organic layer was concentrated down and purified by flash column chromatography (silica gel, 20 to 80% ethyl acetate/hexane) to give 6-[5-(4-Bromo-phenyl)-1H-imidazol-2-yl]-5-aza-spiro[2.4]heptane-5-carboxylic acid tert-butyl ester (249 mg, yield 61%). LCMS-ESI−: calc'd for C20H24BrN3O2: 418.33. Found: 418. (M+H+).

Workup

  1. washwashed
  2. concentrationThe organic layer was concentrated down
  3. custompurified by flash column chromatography (silica gel, 20 to 80% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-e166b3f036334555920f5f6019a394b3
Source dataset
uspto-grants-2014_09
Patent number
US08841278B2

Reaction notes

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