Sulfur Dioxide → HCID 19434100, compound

HRID 1736002Notes

Reaction equation

HRID 1736002 reaction equation
[CH2:1]1[O:10][CH:4]([C:5]2[CH:9]=[CH:8][S:7][CH:6]=2)[O:3][CH2:2]1.C([Li])CCC.[S:16](=[O:18])=[O:17].ClN1C(=O)CCC1=O.Cl.[CH2:28]([O:30][C:31](=[O:35])[CH2:32][NH:33][CH3:34])[CH3:29]>C1COCC1.C(=O)(O)[O-].[Na+]>[CH2:28]([O:30][C:31](=[O:35])[CH2:32][N:33]([S:16]([C:6]1[S:7][CH:8]=[CH:9][C:5]=1[CH:4]1[O:10][CH2:1][CH2:2][O:3]1)(=[O:18])=[O:17])[CH3:34])[CH3:29]

Participants

8

Reactant 5

HCID 1119Sulfur DioxideHCID 31398ChlorosuccinimideHCID 171173Ethyl N-methylaminoacetate hydrochlorideHCID 3156302-(3-Thienyl)-1,3-dioxolaneHCID 178418339Butyllithium

Product 1

HCID 19434100HCID 19434100, compoundYield 72%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
-50 °C

Procedure

To a solution of thiophene-3-carboxaldehyde ethylene acetal (5.82 g, 37.3 mmol) in anhydrous THF (50 mL) at -70° C. was added 2.5M n-butyllithium (16.4 mL, 41 mmol) over 10 min. The solution was stirred at -50° C. for 10 min, cooled to -70° C. for 30 min and sulfur dioxide was passed over the reaction mixture for 5 min. The mixture was allowed to warm to ambient temperature, the volatiles were evaporated and methylene chloride (200 mL) was added. The suspension was cooled (ice bath) and N-chlorosuccinimide (6.47 g, 48.5 mmol) was added. This mixture was stirred at ambient temperature for 2 h, filtered and the filter pad was washed with ethyl acetate (200 mL). The combined filtrates were added to a solution of sarcosine ethyl ester hydrochloride (15.0 g, 97.6 mmol) in saturated aqueous sodium bicarbonate (100 mL) and the mixture stirred for 4 h at ambient temperature. After the organic layer was separated, the aqueous layer was extracted with ethyl acetate (2×100 mL), the combined extracts were dried (MgSO4) and evaporated to dryness. Purification by column chromatography (silica, 30 to 50% ethyl acetate/hexane) gave an oil (8.95 g, 72%).

Workup

  1. temperaturecooled to -70° C. for 30 min
  2. temperatureto warm to ambient temperature
  3. customthe volatiles were evaporated
  4. additionmethylene chloride (200 mL) was added
  5. additionwas added
  6. stirringThis mixture was stirred at ambient temperature for 2 h
  7. filtrationfiltered
  8. washthe filter pad was washed with ethyl acetate (200 mL)
  9. stirringthe mixture stirred for 4 h at ambient temperature
  10. customAfter the organic layer was separated
  11. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
  12. dry with materialthe combined extracts were dried (MgSO4)
  13. customevaporated to dryness
  14. customPurification by column chromatography (silica, 30 to 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-276443473df74470a3419bb55236991f
Source dataset
uspto-grants-1996_07
Patent number
US05538966

Reaction notes

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