Imidazole → HCID 178453986, compound

HRID 470693Notes

Reaction equation

HRID 470693 reaction equation
Br[CH2:2][CH:3]([OH:6])[CH2:4]Br.C(=O)([O-])[O-].[Na+].[Na+].[C:13]([O:17][C:18](=[O:27])[NH:19][C@H:20]1[CH2:25][CH2:24][C@H:23]([NH2:26])[CH2:22][CH2:21]1)([CH3:16])([CH3:15])[CH3:14].N1C=CN=C1.[C:33]([Si:37]([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)([C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1)Cl)([CH3:36])([CH3:35])[CH3:34]>C(OCC)(=O)C.C(O)C>[Si:37]([O:6][CH:3]1[CH2:4][N:26]([C@H:23]2[CH2:22][CH2:21][C@H:20]([NH:19][C:18](=[O:27])[O:17][C:13]([CH3:16])([CH3:14])[CH3:15])[CH2:25][CH2:24]2)[CH2:2]1)([C:33]([CH3:36])([CH3:35])[CH3:34])([C:45]1[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1

Participants

8

Reactant 5

HCID 795ImidazoleHCID 72871,3-Dibromo-2-propanolHCID 10340Sodium CarbonateHCID 94078tert-ButyldiphenylchlorosilaneHCID 178419079HCID 178419079, compound

Product 1

HCID 178453986HCID 178453986, compoundYield 32.1%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8857Ethyl AcetateSolvent

Procedure

1,3-Dibromo-2-propanol (1.70 ml, 16.5 mmol) and sodium carbonate (15.9 g, 150 mmol) were added to an ethanol (300 ml) solution of tert-butyl(trans-4-aminocyclohexyl)carbamate (3.21 g, 15.0 mmol) and the resulting mixture was stirred under heating to reflux overnight. After cooling, insoluble matter was removed by filtration through celite and then the filtrate was concentrated under reduced pressure. The residue was diluted with water, followed by extraction with ethyl acetate. Then the organic layer was washed with brine. The organic layer was dried over anhydrous sodium sulfate and then the solvent was evaporated under reduced pressure. The residue was dissolved in N,N-dimethylformamide (15 ml) and imidazole (2.45 g, 36.0 mmol) and tert-butyldiphenylchlorosilane (4.29 ml, 16.5 mmol) were added under ice cooling. After stirring at room temperature for 1 hour, the reaction mixture was diluted with ethyl acetate and washed with water and brine in that order. The organic layer was dried over anhydrous magnesium sulfate, then the solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography [chloroform:methanol=10:0→10:1 (v/v)] to give 2.45 g (32%) of the title compound as a colorless solid.

Workup

  1. temperatureunder heating
  2. temperatureto reflux overnight
  3. temperatureAfter cooling
  4. custominsoluble matter was removed by filtration through celite
  5. concentrationthe filtrate was concentrated under reduced pressure
  6. additionThe residue was diluted with water
  7. extractionfollowed by extraction with ethyl acetate
  8. washThen the organic layer was washed with brine
  9. dry with materialThe organic layer was dried over anhydrous sodium sulfate
  10. customthe solvent was evaporated under reduced pressure
  11. dissolutionThe residue was dissolved in N,N-dimethylformamide (15 ml)
  12. stirringAfter stirring at room temperature for 1 hour
  13. washwashed with water and brine in that order
  14. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
  15. customthe solvent was evaporated under reduced pressure
  16. customthe residue was purified by silica gel column chromatography [chloroform:methanol=10:0→10:1 (v/v)]

Sources & evidence

ORD record
ord-86272ab71bb749b899e6c1fda16ec9e8
Source dataset
uspto-grants-2014_01
Patent number
US08629133B2

Reaction notes

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