p-Toluenesulfonic acid → Ethyl 2-(4-methoxyphenylmethyl)-2H-thieno[3,2-e]-1,2-thiazine-3-carboxylate 1,1-dioxide

HRID 1736012Notes

Reaction equation

HRID 1736012 reaction equation
[CH2:1]([O:3][C:4](=[O:29])[CH2:5][N:6]([S:16]([C:19]1[S:20][CH:21]=[CH:22][C:23]=1[CH:24]1OCCO1)(=[O:18])=[O:17])[CH2:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1)[CH3:2].C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)(O)[O-].[Na+]>CC(C)=O>[CH3:15][O:14][C:11]1[CH:12]=[CH:13][C:8]([CH2:7][N:6]2[C:5]([C:4]([O:3][CH2:1][CH3:2])=[O:29])=[CH:24][C:23]3[CH:22]=[CH:21][S:20][C:19]=3[S:16]2(=[O:18])=[O:17])=[CH:9][CH:10]=1

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 516892Sodium BicarbonateHCID 53954663N-[[3-(1,3-Dioxolan-2-yl)-2-thienyl]sulfonyl]-N-(4-methoxyphenylmethyl) glycine Ethyl Ester

Product 1

HCID 19434025Ethyl 2-(4-methoxyphenylmethyl)-2H-thieno[3,2-e]-1,2-thiazine-3-carboxylate 1,1-dioxideYield 55%

Reagents, catalysts & solvents 1

HCID 180AcetoneSolvent

Procedure

A mixture of the product from Step A (3.91 g) and p-toluenesulfonic acid (0.2 g) in acetone (150 mL) was heated at reflux temperature for 3 h, cooled and a saturated solution of sodium bicarbonate (50 mL) was added and acetone evaporated. The aqueous mixture was extracted with ethyl acetate (2×10 mL) and the combined extracts were dried (MgSO4) and filtered. DBU (0.3 g) was added to the filtrate and this mixture was heated at reflux temperature for 2 h, cooled and acidified by the addition of 1N HCl. The organic layer was separated, dried (MgSO4) and evaporated to a residue which was purified by column chromatography (silica, 30% ethyl acetate/hexane) to give a viscous oil (1.80 g, 55%).

Workup

  1. temperaturewas heated
  2. temperatureat reflux temperature for 3 h
  3. temperaturecooled
  4. customacetone evaporated
  5. extractionThe aqueous mixture was extracted with ethyl acetate (2×10 mL)
  6. dry with materialthe combined extracts were dried (MgSO4)
  7. filtrationfiltered
  8. additionDBU (0.3 g) was added to the filtrate
  9. temperaturethis mixture was heated
  10. temperatureat reflux temperature for 2 h
  11. temperaturecooled
  12. additionacidified by the addition of 1N HCl
  13. customThe organic layer was separated
  14. dry with materialdried (MgSO4)
  15. customevaporated to a residue which
  16. customwas purified by column chromatography (silica, 30% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-b69505d19f074356943237d7d0714f43
Source dataset
uspto-grants-1996_07
Patent number
US05538966

Reaction notes

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