Lithium Hexamethyldisilazide → HCID 57987540, compound

HRID 1869748Notes

Reaction equation

HRID 1869748 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[CH3:11][O:12][C:13](=[O:31])[CH2:14][C:15]1[CH:20]=[CH:19][N:18]=[C:17]([C:21]2[CH:26]=[CH:25][C:24]([C:27]([F:30])([F:29])[F:28])=[CH:23][CH:22]=2)[CH:16]=1.Cl[CH2:33]/[CH:34]=[CH:35]\[CH2:36]Cl>C1COCC1>[F:29][C:27]([F:30])([F:28])[C:24]1[CH:23]=[CH:22][C:21]([C:17]2[CH:16]=[C:15]([C:14]3([C:13]([O:12][CH3:11])=[O:31])[CH2:36][CH:35]=[CH:34][CH2:33]3)[CH:20]=[CH:19][N:18]=2)=[CH:26][CH:25]=1

Participants

5

Reactant 3

HCID 2733832Lithium HexamethyldisilazideHCID 64321151,4-Dichloro-cis-2-buteneHCID 46942028HCID 46942028, compound

Product 1

HCID 57987540HCID 57987540, compoundYield 47.1%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Lithium bis(trimethylsilyl)amide (1.0M in THF, 3.8 ml, 3.8 mmol) was added slowly to a stirred solution of the ester from Example 3, Step 2, (509 mg, 1.7 mmol) in dry THF (8 ml) under N2 such that the internal temperature <−70° C. After 30 minutes cis-1,4-dichloro-2-butene (210 μl, 2.0 mmol) was added. The reaction was maintained at this temperature for 30 minutes, then transferred to an ice bath. After 90 minutes the reaction was removed from the cooling bath and stirred at room temperature for 30 minutes, then quenched with saturated aqueous NH4Cl. The mixture was partitioned between EtOAc/H2O. The aqueous layer was extracted with EtOAc (×2). The combined extracts were washed with brine (×1), dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica, eluting with 8% EtOAc/isohexane to give the title compound (278 mg, 47%) as an oil, which solidified on standing. 1H NMR (400 MHz, CDCl3) δ: 2.81 (2H, d, J 15.2), 3.44 (2H, d, J 15.3), 3.70 (3H, s), 5.79 (2H, s), 7.22 (2H, d, J 4.4), 7.66 (1H, s), 7.73 (2H, d, J 8.1), 8.08 (2H, d, J 8.1), 8.63-8.67 (2H, d, J 5.1); M/Z (ES+) 348 (MH+).

Workup

  1. temperatureThe reaction was maintained at this temperature for 30 minutes
  2. customtransferred to an ice bath
  3. customAfter 90 minutes the reaction was removed from the cooling bath
  4. customquenched with saturated aqueous NH4Cl
  5. customThe mixture was partitioned between EtOAc/H2O
  6. extractionThe aqueous layer was extracted with EtOAc (×2)
  7. washThe combined extracts were washed with brine (×1)
  8. dry with materialdried (Na2SO4)
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was purified by chromatography on silica
  12. washeluting with 8% EtOAc/isohexane

Sources & evidence

ORD record
ord-11ae170a637b43258448e65678355812
Source dataset
uspto-grants-2009_12
Patent number
US07638629B2

Reaction notes

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