Potassium Carbonate → 7-Bromo-1-[2-(tert-butyldimethyl-silanyloxy)-propyl]-6-oxiranylmethoxy-1H-indazole

HRID 2121876Notes

Reaction equation

HRID 2121876 reaction equation
[Br:1][C:2]1[C:3]([OH:22])=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][CH:12]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:17])[CH3:16])[CH3:13])[N:8]=[CH:7]2.C(=O)([O-])[O-].[K+].[K+].[CH2:29]([CH:31]1[O:33][CH2:32]1)Br>CC(C)=O>[Br:1][C:2]1[C:3]([O:22][CH2:29][CH:31]2[CH2:32][O:33]2)=[CH:4][CH:5]=[C:6]2[C:10]=1[N:9]([CH2:11][CH:12]([O:14][Si:15]([C:18]([CH3:21])([CH3:20])[CH3:19])([CH3:16])[CH3:17])[CH3:13])[N:8]=[CH:7]2

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 18430Epibromohydrin2×HCID 1358436497-Bromo-1-[2-(tert-butyldimethyl-silanyloxy)-propyl]-1H-indazol-6-ol

Product 1

HCID 224965867-Bromo-1-[2-(tert-butyldimethyl-silanyloxy)-propyl]-6-oxiranylmethoxy-1H-indazoleYield 74%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A suspension of the product from Step C (4.47 g, 11.6 mmol), potassium carbonate (2.25 g, 16 mmol), and epibromohydrine (1.59 mL, 19 mmol) in acetone (230 mL) was heated at reflux for 20 h. Additional epibromohydrine (1.5 mL, 17.9 mmol) was added and the mixture heated at reflux for 18 h. The solid was removed by filtration and the filtrate was concentrated to an oil which was dissolved in EtOAc (150 mL). This solution was washed with saturated aqueous ammonium acetate (150 mL), dried (MgSO4), is and evaporated to a residue which was purified by chromatography (silica, 2% to 10% EtOAc/hexane) to afford an oil (3.77 g, 74%): LC/MS (+APCI) m/z 441, 443 (M+H).

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 20 h
  3. temperaturethe mixture heated
  4. temperatureat reflux for 18 h
  5. customThe solid was removed by filtration
  6. concentrationthe filtrate was concentrated to an oil which
  7. dissolutionwas dissolved in EtOAc (150 mL)
  8. washThis solution was washed with saturated aqueous ammonium acetate (150 mL)
  9. dry with materialdried (MgSO4)
  10. customevaporated to a residue which
  11. customwas purified by chromatography (silica, 2% to 10% EtOAc/hexane)

Sources & evidence

ORD record
ord-9075048e442b4bbdbcfde7f3c9d66333
Source dataset
uspto-grants-2004_02
Patent number
US06696476B2

Reaction notes

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