Lithium Hexamethyldisilazide → HCID 21476927, compound

HRID 2293584Notes

Reaction equation

HRID 2293584 reaction equation
[CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH2:10][C:11]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[O:12])=[CH:4][C:3]=2[O:2]1.C[Si]([N-][Si](C)(C)C)(C)C.[Li+].Br[CH2:37][C:38]1[CH:47]=[CH:46][C:41]([C:42]([O:44][CH3:45])=[O:43])=[CH:40][C:39]=1[CH2:48][CH2:49][CH3:50]>CS(C)=O.C1COCC1>[CH2:1]1[O:9][C:8]2[CH:7]=[CH:6][C:5]([CH:10]([CH2:37][C:38]3[CH:47]=[CH:46][C:41]([C:42]([O:44][CH3:45])=[O:43])=[CH:40][C:39]=3[CH2:48][CH2:49][CH3:50])[C:11]([NH:13][S:14]([C:17]3[CH:22]=[CH:21][C:20]([CH:23]([CH3:25])[CH3:24])=[CH:19][CH:18]=3)(=[O:16])=[O:15])=[O:12])=[CH:4][C:3]=2[O:2]1

Participants

6

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 21476913HCID 21476913, compoundHCID 21476920HCID 21476920, compound

Product 1

HCID 21476927HCID 21476927, compound

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolvent2×HCID 8028TetrahydrofuranSolvent2×

Procedure

To a magnetically stirred solution of 0.531 g (1.47 mmol) of the product of Example 1 dissolved in 2.0 mL of DMSO was added 4.40 mL of a 1.0M solution of lithium bis(trimethylsilyl)amide in THF under a nitrogen atmosphere at a temperature just warm enough to prevent the DMSO from solidifying (approximately 18° C.). During the addition of the base, the reaction mixture was further cooled to 0°-50° C. with an ice-water bath. When the addition was complete, the reaction mixture was stirred for 1 hour at 0°-5° C., then a solution of 0.496 g (1.84 mmol) of the product of Step E dissolved in 2.0 mL of THF was added via syringe. The ice-water bath was then removed and the reaction mixture was stirred at room temperature for an additional hour. The mixture was next partitioned between EtOAc and 10% aqueous NaHSO4, and extracted. The organic layer was separated, washed with saturated brine, dried (MgSO4), filtered, and evaporated. The residue was partially purified on a silica gel flash chromatography column eluted with 1% MeOH--CHCl3. After evaporation of the product containing fractions the residue was rechromatographed on a silica gel flash chromatography column eluted with 5% EtOAc--CHCl3. Evaporation of the product containing fractions and drying in vacuo afforded 0.284 (36%) of the title compound as an amorphous white solid.

Workup

  1. temperaturejust warm enough
  2. customfrom solidifying (approximately 18° C.)
  3. additionDuring the addition of the base
  4. temperaturethe reaction mixture was further cooled to 0°-50° C. with an ice-water bath
  5. additionWhen the addition
  6. additionwas added via syringe
  7. customThe ice-water bath was then removed
  8. stirringthe reaction mixture was stirred at room temperature for an additional hour
  9. customThe mixture was next partitioned between EtOAc and 10% aqueous NaHSO4
  10. extractionextracted
  11. customThe organic layer was separated
  12. washwashed with saturated brine
  13. dry with materialdried (MgSO4)
  14. filtrationfiltered
  15. customevaporated
  16. customThe residue was partially purified on a silica gel flash chromatography column
  17. washeluted with 1% MeOH
  18. customAfter evaporation of the product
  19. additioncontaining fractions the residue
  20. customwas rechromatographed on a silica gel flash chromatography column
  21. washeluted with 5% EtOAc
  22. customEvaporation of the product
  23. additioncontaining fractions
  24. customdrying in vacuo

Sources & evidence

ORD record
ord-3f5992d4863445ada236d2219ab956bd
Source dataset
uspto-grants-1997_11
Patent number
US05686478

Reaction notes

Loading…