Hydrochloric Acid → HCID 19074412, compound

HRID 964943Notes

Reaction equation

HRID 964943 reaction equation
[H-].[Na+].C1[O:18][C:6]2([C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[S:9](=[O:17])(=[O:16])[NH:8][CH2:7]2)OC1.[CH2:19]([O:26][CH:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][CH2:35]Cl)[CH2:29][CH2:28]1)[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.Cl>COCCOC.C(Cl)(Cl)Cl.CO.CO>[CH2:19]([O:26][CH:27]1[CH2:32][CH2:31][N:30]([CH2:33][CH2:34][CH2:35][N:8]2[CH2:7][C:6](=[O:18])[C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[S:9]2(=[O:16])=[O:17])[CH2:29][CH2:28]1)[C:20]1[CH:21]=[CH:22][CH:23]=[CH:24][CH:25]=1

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 19074433HCID 19074433, compoundHCID 218178932H-1,2-benzothiazin-4(3H)-one 1,1-dioxide ethylene ketal

Product 1

HCID 19074412HCID 19074412, compoundYield 48.9%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 80711,2-DimethoxyethaneSolvent2×HCID 21584188Chloroform methanolSolvent

Conditions

Temperature
50 °C

Procedure

In 1,2-dimethoxyethane (40 mL) was suspended 60% sodium hydride (180 mg, 4.5 mmol.), and then 2H-1,2-benzothiazin-4(3H)-one 1,1-dioxide ethylene ketal (1.00 g, 4.1 mmol.) was added to the suspension. The suspension was heated for 1 hour under stirring. The reaction liquid was cooled to 50° C., and to this was added a solution of 4-benzyloxy-1-(3-chloropropyl)piperidine (1.11 g, 4.1 mmol.) in 1,2-dimethoxyethane (10 mL). The mixture was further heated for 20 hours under refluxing. The reaction liquid was filtered to remove insolubles and the solvent was distilled off to give a residue. To the residue were added aqueous 9% hydrochloric acid (30 mL) and methanol (30 mL), and the mixture was heated for 15 min. under refluxing. The reaction liquid was placed under reduced pressure to distill methanol off. The residue was treated with ice-water, and the deposited oil was extracted with dichloromethane. The dichloromethane portion was washed with water and an aqueous saturated sodium chloride solution, and dried over anhydrous sodium sulfate. The solvent was distilled off to leave a residue. The residue was treated by silica gel column chromatography (chloroform/methanol=30/1) to give the desired compound (860 mg, yield 45%) as a red oil.

Workup

  1. temperatureThe suspension was heated for 1 hour
  2. customThe reaction liquid
  3. temperatureThe mixture was further heated for 20 hours
  4. temperatureunder refluxing
  5. customThe reaction liquid
  6. filtrationwas filtered
  7. customto remove insolubles
  8. distillationthe solvent was distilled off
  9. customto give a residue
  10. temperaturethe mixture was heated for 15 min.
  11. temperatureunder refluxing
  12. customThe reaction liquid
  13. distillationto distill methanol off
  14. additionThe residue was treated with ice-water
  15. extractionthe deposited oil was extracted with dichloromethane
  16. washThe dichloromethane portion was washed with water
  17. dry with materialan aqueous saturated sodium chloride solution, and dried over anhydrous sodium sulfate
  18. distillationThe solvent was distilled off
  19. customto leave a residue

Sources & evidence

ORD record
ord-5a09ea36f5824b1ab36956377b99a41f
Source dataset
uspto-grants-1998_06
Patent number
US05773437

Reaction notes

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