Imidazole → HCID 54489812, compound

HRID 2399863Notes

Reaction equation

HRID 2399863 reaction equation
[CH2:1]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][CH:10]=1)[C:2]1[CH:7]=CC=CC=1.[Si:16](Cl)([C:19]([CH3:22])([CH3:21])[CH3:20])([CH3:18])[CH3:17].N1C=CN=C1.[H-].[Na+].CN(C)C=[O:34]>C(OCC)(=O)C.[OH-].[OH-].[Pd+2]>[CH3:20][C:19]([Si:16]([CH3:18])([CH3:17])[O:15][C:12]1[CH:11]=[CH:10][C:9]([O:8][CH2:1][C@@H:2]2[CH2:7][O:34]2)=[CH:14][CH:13]=1)([CH3:22])[CH3:21]

Participants

8

Reactant 5

HCID 795ImidazoleHCID 6228Dimethylformamide3×HCID 7638MonobenzoneHCID 24758Sodium hydrideHCID 28928tert-Butyldimethylsilyl chloride

Product 1

HCID 54489812HCID 54489812, compound

Reagents, catalysts & solvents 2

HCID 9942167Palladium hydroxideCatalystHCID 8857Ethyl AcetateSolvent2×

Procedure

A solution of 10.0 g (50.0 mmol) of 4-benzyloxyphenol, 9.04 g (60.0 mmol) of tert-butyldimethylsilyl chloride, and 4.42 g (65.0 mmol) of imidazole in dimethylforamide (DMF) was allowed to stir at ambient temperature overnight. The mixture was then diluted with ethyl acetate, washed sequentially with water, 1 M aqueous sodium bisulfate solution, 1 M aqueous sodium hydroxide solution, and brine, dried over magnesium sulfate, and concentrated to give a white solid. The unpurified compound was dissolved in 40 mL of ethyl acetate and allowed to stir over 20% palladium hydroxide on carbon under an atmosphere of hydrogen overnight. The reaction mixture was then filtered through a pad of Celite and concentrated. The resultant phenol was dissolved in 40 mL of DMF and added dropwise over a 30-min period via cannula to a mixture of 2.60 g (65.0 mmol) of sodium hydride (60% dispersion in mineral oil) at 0° C. A 10-mL portion of DMF was added. After the mixture was allowed to stir at 0° C. for 30 min, a solution of 14.3 g (55.0 mmol) of (2S)-glycidyl 3-nitrobenzene sulfonate in 40 mL of DMF was added dropwise over a 20-min period. After the reaction was judged to be complete by TLC analysis, it was quenched with water, diluted with ethyl acetate, washed sequentially with water, 1 M aqueous sodium hydroxide solution, and brine, dried over magnesium sulfate, and concentrated. Purification by flash chromatography (silica gel, 10% ethyl acetate/hexane) gave 5.04 g (36% overall yield) of the title compound: 1H NMR (400 MHz, CD3OD) δ6.82 (d, 2H, J=9.1 Hz), 6.74 (d, 2H, J=9.1 Hz), 4.22 (dd, 1 H, J=2.6, 11.2 Hz), 3.79 (dd, 1H, J=6.2, 11.2 Hz), 3.30 (m, 1H), 2.84 (t, 1 H, J=4.6 Hz), 2.71 (dd, 1H, J=2.7, 5.0 Hz), 0.97 (s, 9H), 0.15 (s, 6H).

Workup

  1. washwashed sequentially with water, 1 M aqueous sodium bisulfate solution, 1 M aqueous sodium hydroxide solution, and brine
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated
  4. customto give a white solid
  5. filtrationThe reaction mixture was then filtered through a pad of Celite
  6. concentrationconcentrated
  7. dissolutionThe resultant phenol was dissolved in 40 mL of DMF
  8. stirringto stir at 0° C. for 30 min
  9. customwas quenched with water
  10. additiondiluted with ethyl acetate
  11. washwashed sequentially with water, 1 M aqueous sodium hydroxide solution, and brine
  12. dry with materialdried over magnesium sulfate
  13. concentrationconcentrated
  14. customPurification by flash chromatography (silica gel, 10% ethyl acetate/hexane)
  15. customgave

Sources & evidence

ORD record
ord-9ecc0c5781df44ff8607738154dfa76a
Source dataset
uspto-grants-1995_09
Patent number
US05451677

Reaction notes

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