Dimethyl Disulfide → HCID 19738114, compound

HRID 2255417Notes

Reaction equation

HRID 2255417 reaction equation
[CH3:1][N:2]1[CH:7]([CH3:8])[C:6]2([CH3:12])[CH:9]([CH3:11])[CH2:10][CH:3]1[CH:4]([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:5]2.C([N-]C(C)C)(C)C.[Li+].[CH3:26][S:27]SC.[NH4+].[Cl-]>C1COCC1>[CH3:1][N:2]1[CH:7]([CH3:8])[C:6]2([CH3:12])[CH:9]([CH3:11])[CH2:10][CH:3]1[C:4]([S:27][CH3:26])([C:13]([O:15][CH2:16][CH3:17])=[O:14])[CH2:5]2

Participants

6

Reactant 4

HCID 12232Dimethyl DisulfideHCID 25517Ammonium ChlorideHCID 2724682Lithium diisopropylamideHCID 19097385HCID 19097385, compound

Product 1

HCID 19738114HCID 19738114, compoundYield 81%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A solution of diisopropylamine (6.8 mL, 48 mmol) in THF (100 mL) was cooled to -70° C. and n-BuLi (17.6 mL, 44 mmol, 2.5M hexane) was added to afford lithium diisopropylamide (LDA). A solution of ethyl 2,3,4,8-tetramethyl-2-azabicyclo[2.2.2]octane-6-carboxylate (9.6 g, 40 mmol) in THF (50 mL) was then added dropwise to the solution of LDA and the mixture was stirred for 2.5 hours. Methyl disulfide (4.3 mL, 48 mmol) was then added to the reaction mixture and the mixture was slowly warmed to room temperature and was stirred for 16 hours. The mixture was poured into saturated NH4Cl (200 mL), the organic layer was separated and the aqueous layer was extracted with ether (2×200 mL). The organic layers were combined, dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was purified by medium pressure liquid chromatography (10-15% ethyl acetate/hexane) to afford 9.2 g (81%) of ethyl 2,3,4,8-tetramethyl-6-(methylthio)-2-azabicyclo[2.2.2]octane-6-carboxylate. The product was dissolved in ether and treated with ethereal HCl to afford 6.5 g of the hydrochloride salt as a white powder, m.p. 143°-145° C. when recrystallized from ethyl acetate.

Workup

  1. stirringwas stirred for 16 hours
  2. customthe organic layer was separated
  3. extractionthe aqueous layer was extracted with ether (2×200 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by medium pressure liquid chromatography (10-15% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-f5548d5965214ece82f9a201401fead5
Source dataset
uspto-grants-1993_08
Patent number
US05240935

Reaction notes

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