Imidazole → HCID 11223219, compound

HRID 1784169Notes

Reaction equation

HRID 1784169 reaction equation
[C:1]1([S:7]([CH:10]2[CH:16]=[C:15](SC3C=CC=CC=3)[CH2:14][CH2:13][C@@H:12]([O:24][Si](C)(C)C)[C@H:11]2[CH3:29])(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[CH3:30][C:31]([Si:34](Cl)([CH3:36])[CH3:35])([CH3:33])[CH3:32].N1C=CN=C1.C1C[O:46]CC1.CCCC[N+](CCCC)(CCCC)CCCC.[F-]>CN(C=O)C>[C:1]1([S:7]([C:10]2[C@H:11]([CH3:29])[C@@H:12]([O:24][Si:34]([C:31]([CH3:33])([CH3:32])[CH3:30])([CH3:36])[CH3:35])[C@@H:14]([CH3:13])[C@H:15]([OH:46])[CH:16]=2)(=[O:8])=[O:9])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

7

Reactant 5

HCID 795ImidazoleHCID 8028TetrahydrofuranHCID 28928tert-Butyldimethylsilyl chlorideHCID 2724141Tetrabutylammonium FluorideHCID 10321368HCID 10321368, compound

Product 1

HCID 11223219HCID 11223219, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

The mixture of diol 23 (585 mg, 2.07 mmol), TBSCl (1.0 g, 6.63 mmol), and imidazole (564 mg, 8.28 mmol) in DMF (5.0 mL) was stirred at 70° C. for 20 h under nitrogen. After being quenched by aqueous NH4Cl, the reaction mixture was extracted with diethyl ether (3×20 mL). The organic layers were washed with brine, dried over Na2SO4, concentrated via rotary evaporation, and further dried in vacuo. The crude residue was dissolved in THF (20 mL), and a THF solution (2.3 mL, 2.3 mmol, 1M) of TBAF was added at room temperature. After being stirred at room temperature for 30 min, the solution was quenched with aqueous NH4Cl solution, and the product was extracted with ethyl acetate (3×10 mL). The organic layers were dried over Na2SO4 and concentrated via rotary evaporation. The crude product was purified by flash column chromatography (ethyl acetate/hexanes; 1:4) to afford 690 mg (84%) of 38 as a white solid. Mp 106.6-108.5° C.; 1H NMR (CDCl3, 300 MHz): δ 7.86 (d, J=7.5 Hz, 2H), 7.48-7.62 (m, 3H), 7.00 (d, J=2.1 Hz, 1H), 4.13 (d, J=9.3 Hz, 1H), 3.54 (s, 1H), 2.27 (q, J=6.9 Hz, 1H), 2.01 (s, 1H), 1.78 (m, 1H), 1.24 (d, J=7.2 Hz, 3H), 1.09 (d, J=6.3 Hz, 3H), 0.64 (s, 9H), −0.06 (s, 3H), −0.35 (s, 3H); 13C NMR (CDCl3, 75 MHz): δ 142.8, 140.4, 139.4, 133.3, 129.2, 128.2, 77.9, 70.7, 37.7, 36.3, 25.6, 18.5, 17.7, 14.9, −4.7, −5.3. Anal. Calcd for C20H32O4SSi: C, 60.57; H, 8.13. Found: C, 60.82; H, 8.07.

Workup

  1. customAfter being quenched by aqueous NH4Cl
  2. extractionthe reaction mixture was extracted with diethyl ether (3×20 mL)
  3. washThe organic layers were washed with brine
  4. dry with materialdried over Na2SO4
  5. concentrationconcentrated via rotary evaporation
  6. customfurther dried in vacuo
  7. dissolutionThe crude residue was dissolved in THF (20 mL)
  8. stirringAfter being stirred at room temperature for 30 min
  9. customthe solution was quenched with aqueous NH4Cl solution
  10. extractionthe product was extracted with ethyl acetate (3×10 mL)
  11. dry with materialThe organic layers were dried over Na2SO4
  12. concentrationconcentrated via rotary evaporation
  13. customThe crude product was purified by flash column chromatography (ethyl acetate/hexanes; 1:4)

Sources & evidence

ORD record
ord-ddf938e6d3e84ba59942c28c81d2961f
Source dataset
uspto-grants-2009_03
Patent number
US07501535B2

Reaction notes

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