Imidazole → HCID 178455354, compound

HRID 1631431Notes

Reaction equation

HRID 1631431 reaction equation
[OH:1][C@H:2]1[CH2:7][CH2:6][C@H:5]([N:8]2[C:16](=[O:17])[C:15]3[C:10](=[CH:11][CH:12]=[CH:13][CH:14]=3)[C:9]2=[O:18])[CH2:4][CH2:3]1.N1C=CN=C1.[C:24]([Si:28](Cl)([CH3:30])[CH3:29])([CH3:27])([CH3:26])[CH3:25]>CN(C=O)C.C1(C)C=CC=CC=1.O>[Si:28]([O:1][C@H:2]1[CH2:3][CH2:4][C@H:5]([N:8]2[C:9](=[O:18])[C:10]3[C:15](=[CH:14][CH:13]=[CH:12][CH:11]=3)[C:16]2=[O:17])[CH2:6][CH2:7]1)([C:24]([CH3:27])([CH3:26])[CH3:25])([CH3:30])[CH3:29]

Participants

7

Reactant 3

HCID 795ImidazoleHCID 28928tert-Butyldimethylsilyl chloride2×HCID 178515017HCID 178515017, compound

Product 1

HCID 178455354HCID 178455354, compoundYield 96%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 1140TolueneSolvent2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
40 °C

Procedure

To a stirred solution of 12A (6.5 g, 26.5 mmol) in DMF (20 mL) was added imidazole (3.61 g, 53.0 mmol), followed by tert-butylchlorodimethylsilane in toluene (9.22 mL, 26.5 mmol) portionwise while cooling with an ice bath. Upon completion of the addition, the resulting mixture was stirred at 40° C. for 3 h. There was still some starting material left, so more 50% tert-butylchlorodimethylsilane in toluene (2.5 mL) was added, and the mixture was stirred briefly at room temperature. The mixture was diluted with water and extracted with hexane (3×). The combined organic extracts were washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to provide 12B (9.1 g, 96% yield) as a white solid. MS (ES): m/z=360.1 [M+H]+. 1H NMR (400 MHz, CDCl3) δ ppm 7.74 (dd, 2H, J=5.5, 3.1 Hz); 7.62 (dd, 2H, J=5.5, 3.1 Hz); 3.96-4.15 (m, 1H); 3.56-3.72 (m, 1H); 2.17-2.29 (m, 2H); 1.85-1.92 (m, 2H); 1.61-1.69 (m, 2H); 1.31-1.43 (m, 2H); 0.82 (s, 9H); 0.00 (s, 6H).

Workup

  1. temperaturewhile cooling with an ice bath
  2. additionUpon completion of the addition
  3. waitleft
  4. stirringthe mixture was stirred briefly at room temperature
  5. extractionextracted with hexane (3×)
  6. washThe combined organic extracts were washed with brine
  7. dry with materialdried over anhydrous magnesium sulfate
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-1a7b8a0a2e5b48039aed2e5c5ab02dfa
Source dataset
uspto-grants-2014_07
Patent number
US08791257B2

Reaction notes

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