Triethylamine → [6-(Tert-butyl-diphenyl-silanyloxymethyl)-2-methyl-imidazo[1,2-a]pyridin-3-yl]-acetic acid ethyl ester

HRID 216677Notes

Reaction equation

HRID 216677 reaction equation
[CH2:1]([O:3][C:4](=[O:11])[CH2:5][CH:6](Br)[C:7](=O)[CH3:8])[CH3:2].C(N(CC)CC)C.[C:19]([SiH2:23][O:24][C:25]([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)([C:33]1[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=1)[C:26]1[CH:27]=[CH:28][C:29]([NH2:32])=[N:30][CH:31]=1)([CH3:22])([CH3:21])[CH3:20]>C(O)(C)C>[CH2:1]([O:3][C:4](=[O:11])[CH2:5][C:6]1[N:30]2[CH:31]=[C:26]([C:25]([C:33]3[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=3)([C:39]3[CH:40]=[CH:41][CH:42]=[CH:43][CH:44]=3)[O:24][SiH2:23][C:19]([CH3:22])([CH3:20])[CH3:21])[CH:27]=[CH:28][C:29]2=[N:32][C:7]=1[CH3:8])[CH3:2]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 12933940Ethyl 3-bromo-4-oxopentanoateHCID 178455411HCID 178455411, compound

Product 1

HCID 131729756[6-(Tert-butyl-diphenyl-silanyloxymethyl)-2-methyl-imidazo[1,2-a]pyridin-3-yl]-acetic acid ethyl esterYield 55%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Procedure

3-Bromo-4-oxo-pentanoic acid ethyl ester (1.77 g, 7.86 mmol, 2.0 equiv) and triethylamine (1.10 ml, 7.86 mmol, 2.0 equiv) are added to a solution of 5-(tert-butyl-diphenyl-silanyloxymethyl)-pyridin-2-ylamine in iso-propanol (10 ml). The reaction mixture is heated to reflux for 5 hours. After cooling, volatiles are removed in vacuo. The residue is taken up with water and EtOAc. The aqueous phase is extracted three times with EtOAc. The combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated in vacuo. Purification via flash chromatography (hexane/AcOEt 1:1 to 1:4) affords the title compound (1.10 g, 55%). MS (ES+): 487 (M+H)+.

Workup

  1. temperatureThe reaction mixture is heated
  2. temperatureto reflux for 5 hours
  3. temperatureAfter cooling
  4. customvolatiles are removed in vacuo
  5. extractionThe aqueous phase is extracted three times with EtOAc
  6. washThe combined organic layers are washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customPurification via flash chromatography (hexane/AcOEt 1:1 to 1:4)

Sources & evidence

ORD record
ord-cd40b8affff942c5991c0204c264ee96
Source dataset
uspto-grants-2012_06
Patent number
US08193236B2

Reaction notes

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