Morpholine → 2-(3-Methoxypropyl)-3-(4-morpholinylmethyl)-2H-thieno[3,2-e]-1,2-thiazine-1,1-dioxide

HRID 1736010Notes

Reaction equation

HRID 1736010 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:11]([CH2:12]O)=[CH:10][C:9]2[CH:14]=[CH:15][S:16][C:8]=2[S:7]1(=[O:18])=[O:17].C(N(CC)CC)C.CS(OS(C)(=O)=O)(=O)=O.[NH:35]1[CH2:40][CH2:39][O:38][CH2:37][CH2:36]1>C1COCC1>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][N:6]1[C:11]([CH2:12][N:35]2[CH2:40][CH2:39][O:38][CH2:37][CH2:36]2)=[CH:10][C:9]2[CH:14]=[CH:15][S:16][C:8]=2[S:7]1(=[O:18])=[O:17]

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 81560Methanesulfonic anhydrideHCID 194341212-(3-Methoxypropyl)-2H-thieno[3,2-e]-1,2-thiazine-3-methanol 1,1-dioxide

Product 1

HCID 194341012-(3-Methoxypropyl)-3-(4-morpholinylmethyl)-2H-thieno[3,2-e]-1,2-thiazine-1,1-dioxideYield 94%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of the product from Step C (1.30 g, 4.50 mmol) and triethylamine (1.36 g, 13.5 mmol) in anhydrous THF (30 mL) at ambient temperature was added methanesulfonic anhydride (1.18 g, 6.75 mmol). After stirring for 30 min, morpholine (5 mL) was added; this mixture was stirred at ambient temperature for 18 h and then heated at reflux for 1 h. The volatiles were evaporated and a saturated aqueous solution of sodium bicarbonate (100 mL) was added. The mixture was extracted with ethyl acetate (2×100 mL) and the combined extracts were dried (MgSO4) and evaporated to give a viscous oil which was purified by column chromatography (silica, 30 to 50% ethyl acetate/hexane) to give a viscous oil (1.51 g, 94%).

Workup

  1. stirringthis mixture was stirred at ambient temperature for 18 h
  2. temperatureheated
  3. temperatureat reflux for 1 h
  4. customThe volatiles were evaporated
  5. additiona saturated aqueous solution of sodium bicarbonate (100 mL) was added
  6. extractionThe mixture was extracted with ethyl acetate (2×100 mL)
  7. dry with materialthe combined extracts were dried (MgSO4)
  8. customevaporated
  9. customto give a viscous oil which
  10. customwas purified by column chromatography (silica, 30 to 50% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-03540382433b40899ddd5ddbe0db2214
Source dataset
uspto-grants-1996_07
Patent number
US05538966

Reaction notes

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