Imidazole → HCID 58638077, compound

HRID 1768459Notes

Reaction equation

HRID 1768459 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C:9]1[CH2:17][N:12]2C(=O)[O:14][CH2:15][C:11]2([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:10]=1.CCOC(C)=O.N1C=CN=C1.[CH3:35][C:36]([Si:39](Cl)([CH3:41])[CH3:40])([CH3:38])[CH3:37]>CCO.[OH-].[Na+].[Cl-].[Na+].O.C(Cl)Cl>[Si:39]([O:14][CH2:15][C:11]1([C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)[CH:10]=[C:9]([C:3]2[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=2[F:1])[CH2:17][NH:12]1)([C:36]([CH3:38])([CH3:37])[CH3:35])([CH3:41])[CH3:40]

Participants

9

Reactant 4

HCID 795ImidazoleHCID 8857Ethyl AcetateHCID 28928tert-Butyldimethylsilyl chlorideHCID 23614741HCID 23614741, compound

Product 1

HCID 58638077HCID 58638077, compound

Reagents, catalysts & solvents 4

HCID 702EthanolSolventHCID 6344DichloromethaneSolvent2×HCID 14798Sodium HydroxideSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
60 °C

Procedure

A suspension of 1.75 g (5.6 mmol) 1-7 in 15 mL of EtOH and 10 mL of 3 M NaOH was heated at 60° C. for 3 h, cooled to room temperature and dumped into a separatory funnel with EtOAc and brine. The layers were separated, the aqueous phase was extracted twice with EtOAc, the combined organic phases were washed twice with brine, dried over Na2SO4, and concentrated to provide a white solid. To this flask was added 30 mL of CH2Cl2, 1.5 g (22.3 mmol) of imidazole and 1.76 g (11.7 mmol) of TBSCl, and the resultant suspension was stirred overnight. The reaction was diluted with CH2Cl2, washed twice with water, dried over Na2SO4, concentrated, and the residue purified by silica gel chromatography with EtOAc/hexanes to provide 1-8 as a white solid. Data for 1-8: 1HNMR (500 MHz, CDCl3) δ 7.6-7.3 (m, 5H), 7.1-6.9 (m, 3H), 6.75 (s, 1H), 4.25 (d, 1H), 4.1 (d, 1H), 3.95 (d, 1H), 3.75 (d, 1H), 0.9 (s, 9H), 0.1 (s, 3H), 0.05 (s, 3H) ppm.

Workup

  1. temperaturecooled to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous phase was extracted twice with EtOAc
  4. washthe combined organic phases were washed twice with brine
  5. dry with materialdried over Na2SO4
  6. concentrationconcentrated
  7. customto provide a white solid
  8. washwashed twice with water
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated
  11. customthe residue purified by silica gel chromatography with EtOAc/hexanes

Sources & evidence

ORD record
ord-bab1358b8c224a42b4a64a3ec234ac60
Source dataset
uspto-grants-2007_06
Patent number
US07235580B2

Reaction notes

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