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

HRID 1736017Notes

Reaction equation

HRID 1736017 reaction equation
CS(OS(C)(=O)=O)(=O)=O.O[CH2:11][C:12]1(CO)[CH2:17][C:16]2[CH:18]=[CH:19][S:20][C:15]=2[S:14](=[O:22])(=[O:21])[N:13]1[CH2:23][C:24]1[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=1.C(N(CC)CC)C.[NH:41]1[CH2:46][CH2:45][O:44][CH2:43][CH2:42]1>C1COCC1>[CH3:31][O:30][C:27]1[CH:28]=[CH:29][C:24]([CH2:23][N:13]2[C:12]([CH2:11][N:41]3[CH2:46][CH2:45][O:44][CH2:43][CH2:42]3)=[CH:17][C:16]3[CH:18]=[CH:19][S:20][C:15]=3[S:14]2(=[O:21])=[O:22])=[CH:25][CH:26]=1

Participants

6

Reactant 4

HCID 8083MorpholineHCID 8471TriethylamineHCID 81560Methanesulfonic anhydrideHCID 677348383-Hydroxymethyl-2-(4-methoxyphenylmethyl)-2H-thieno[3,2-e]-1,2-thiazine-3-methanol 1,1-dioxide

Product 1

HCID 194340692-(4-Methoxyphenylmethyl)-3-(4-morpholinylmethyl)-2H-thieno[3,2-e]-1,2-thiazine 1,1-dioxideYield 88%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methanesulfonic anhydride (1.24 g, 7.13 mmol) was added to a solution of the product of Example 11, Step C (1.3 g, 3.86 mmol) and triethylamine (1.17 g, 11.6 mmol) in anhydrous THF (50 mL) at ambient temperature. After stirring for 1 h, morpholine (3 mL) was added and the reaction mixture was heated at reflux temperature for 1 h followed by removal of solvent. A saturated aqueous solution of sodium bicarbonate was added and the mixture was extracted with ethyl acetate (2×100 mL). The combined extracts were dried (MgSO4) and evaporated to an oil which was purified by column chromatography (silica, 30% to 60% ethyl acetate/hexane) to give a solid (1.39 g, 88%): mp 112°-114° C.

Workup

  1. temperaturethe reaction mixture was heated
  2. temperatureat reflux temperature for 1 h
  3. customfollowed by removal of solvent
  4. additionA saturated aqueous solution of sodium bicarbonate was added
  5. extractionthe mixture was extracted with ethyl acetate (2×100 mL)
  6. dry with materialThe combined extracts were dried (MgSO4)
  7. customevaporated to an oil which
  8. customwas purified by column chromatography (silica, 30% to 60% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-410a0b5106da49e98202a7c19d076176
Source dataset
uspto-grants-1996_07
Patent number
US05538966

Reaction notes

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