Sodium Iodide → Ethyl 2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-3-carboxylate 1,1-dioxide

HRID 1736008Notes

Reaction equation

HRID 1736008 reaction equation
CC(C)([O-])C.[K+].C(O)(C)(C)C.[CH2:12]([O:14][C:15](=[O:31])[CH2:16][NH:17][S:18]([C:21]1[S:22][CH:23]=[CH:24][C:25]=1[CH:26]1OCCO1)(=[O:20])=[O:19])[CH3:13].Br[CH2:33][CH2:34][CH2:35][O:36][CH3:37].[I-].[Na+].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+].C1CN2C(=NCCC2)C1>CN(C=O)C.CC(C)=O.C(OCC)(=O)C>[CH3:37][O:36][CH2:35][CH2:34][CH2:33][N:17]1[C:16]([C:15]([O:14][CH2:12][CH3:13])=[O:31])=[CH:26][C:25]2[CH:24]=[CH:23][S:22][C:21]=2[S:18]1(=[O:19])=[O:20]

Participants

12

Reactant 8

HCID 5238Sodium IodideHCID 6101p-Toluenesulfonic acidHCID 6386tert-ButanolHCID 763491,5-Diazabicyclo(4.3.0)non-5-eneHCID 516892Sodium BicarbonateHCID 5245511-Bromo-3-methoxypropaneHCID 21480494N-[[3-(1,3-dioxolan-2-yl)-2-thienyl]sulfonyl]glycine ethyl esterHCID 23665647Potassium tert-butoxide

Product 1

HCID 19434095Ethyl 2-(3-methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-3-carboxylate 1,1-dioxideYield 54.1%

Reagents, catalysts & solvents 3

HCID 180AcetoneSolvent2×HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of potassium t-butoxide in t-butanol (1M, 15.7 mL, 15.7 mmol) was added to a solution of the product of Step A (4.80 g, 14.95 mmol) in anhydrous DMF (50 mL) at 0° C. followed by 1-bromo-3-methoxypropane (3.43 g, 22.4 mmol) and sodium iodide (0.2 g). The mixture was stirred for 5 h at ambient temperature, poured into ice water (300 mL) and extracted with ethyl acetate (2×200 mL). The combined extracts were dried (MgSO4), filtered and evaporated to give a viscous liquid which was dissolved in acetone (300 mL); p-toluenesulfonic acid (0.4 g) was added and this mixture was heated at reflux temperature for 4.5 h. A saturated aqueous solution of sodium bicarbonate (100 mL) was added to the reaction mixture and acetone was evaporated. The aqueous mixture was extracted with ethyl acetate (2×200 mL) and the combined extracts were dried (MgSO4), filtered and evaporated to give crude aldehyde which was dissolved in ethyl acetate (100 mL). DBN (0.2 g) was added and the mixture heated at reflux temperature for 2 h under nitrogen. The mixture was cooled, quenched with a 2N HCl (50 mL) and extracted with ethyl acetate (2×150 mL). The combined extracts were dried (MgSO4) and evaporated to a syrup which was purified by column chromatography (silica, 30% ethyl acetate/hexane) to give a white solid (2.68 g, 54%): mp 82°-83° C.

Workup

  1. extractionextracted with ethyl acetate (2×200 mL)
  2. dry with materialThe combined extracts were dried (MgSO4)
  3. filtrationfiltered
  4. customevaporated
  5. customto give a viscous liquid which
  6. temperaturethis mixture was heated
  7. temperatureat reflux temperature for 4.5 h
  8. customwas evaporated
  9. extractionThe aqueous mixture was extracted with ethyl acetate (2×200 mL)
  10. dry with materialthe combined extracts were dried (MgSO4)
  11. filtrationfiltered
  12. customevaporated
  13. customto give crude aldehyde which
  14. temperaturethe mixture heated
  15. temperatureat reflux temperature for 2 h under nitrogen
  16. temperatureThe mixture was cooled
  17. customquenched with a 2N HCl (50 mL)
  18. extractionextracted with ethyl acetate (2×150 mL)
  19. dry with materialThe combined extracts were dried (MgSO4)
  20. customevaporated to a syrup which
  21. customwas purified by column chromatography (silica, 30% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9d595d259ffe4f5d82dfb2e0214f653d
Source dataset
uspto-grants-1996_07
Patent number
US05538966

Reaction notes

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