Sulfur Dioxide → 3,4-Dihydro-2-(3-methoxypropyl)-3-methyl-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide

HRID 1768629Notes

Reaction equation

HRID 1768629 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[CH:11]([CH3:12])[CH2:10][C:9]2[CH:13]=[CH:14][S:15][C:8]=2[S:7]1(=[O:17])=[O:16].C([Li])CCC.[S:23](=[O:25])=[O:24].C([O-])(=O)C.[Na+].[NH2:31]OS(O)(=O)=O.C(=O)(O)[O-].[Na+]>C1COCC1>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[CH:11]([CH3:12])[CH2:10][C:9]2[CH:13]=[C:14]([S:23]([NH2:31])(=[O:25])=[O:24])[S:15][C:8]=2[S:7]1(=[O:17])=[O:16]

Participants

8

Reactant 6

HCID 1119Sulfur DioxideHCID 76284hydroxylamine-O-sulfonic acidHCID 516892Sodium BicarbonateHCID 517045Sodium AcetateHCID 229019473,4-Dihydro-2-(3-methoxypropyl)-3-methyl-2H-thieno[3,2-e]-1,2-thiazine 1,1-dioxideHCID 178418339Butyllithium

Product 1

HCID 229019983,4-Dihydro-2-(3-methoxypropyl)-3-methyl-2H-thieno[3,2-e]-1,2-thiazine-6-sulfonamide 1,1-dioxide

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of the product from Step C (890 mg, 3.23 mmol) in THF (8 mL) at -78° C. was added n-butyllithium (2.0 mL of a 2.5M solution, 4.85 mmol). This mixture was stirred at -78° C. for 40 min and sulfur dioxide was added until the solution maintained a pH of 3. The reaction mixture was warmed to room temperature, stirred for 30 min, and evaporated to a residue which was dissolved in water (20 mL). Sodium acetate (795 mg, 9.69 mmol) and hydroxylamine-O-sulfonic acid (1.0 g, 9.69 mmol) were added, the mixture stirred at room temperature for 18 hr, and the pH was adjusted to 8 with sodium bicarbonate. This solution was extracted with ethyl acetate (2×100 mL), the extracts were dried (MgSO4) and evaporated to a residue which was purified by column chromatography (silica, 5:1 methanol/methylene chloride) to give the desired product. Recrystallization from methylene chloride gave a white solid (320 mg, 29%): mp 140° C. Analysis: Calculated for C11H18N2O5S3 : C, 37.27; H, 5.12; N,7.90. Found: C, 37.38; H, 5.18; N, 7.86.

Workup

  1. temperaturemaintained a pH of 3
  2. temperatureThe reaction mixture was warmed to room temperature
  3. stirringstirred for 30 min
  4. customevaporated to a residue which
  5. dissolutionwas dissolved in water (20 mL)
  6. stirringthe mixture stirred at room temperature for 18 hr
  7. extractionThis solution was extracted with ethyl acetate (2×100 mL)
  8. dry with materialthe extracts were dried (MgSO4)
  9. customevaporated to a residue which
  10. customwas purified by column chromatography (silica, 5:1 methanol/methylene chloride)

Sources & evidence

ORD record
ord-9b5c2c01e4c743adac6e681c5d5f19cf
Source dataset
uspto-grants-1995_01
Patent number
US05378703

Reaction notes

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