Hydrochloric Acid → Spiro[naphtho[1,2-b][1,4]oxathiine-2,4'-piperidinium]-5,6-dione chloride

HRID 1665268Notes

Reaction equation

HRID 1665268 reaction equation
[O:1]=[C:2]1[C:11](=O)[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[C:4]([S:13][CH2:14][C:15]2([OH:28])[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]2)=[CH:3]1.FC(F)(F)C(O)=[O:32].[ClH:36]>ClCCl.O1CCOCC1>[Cl-:36].[NH2+:18]1[CH2:17][CH2:16][C:15]2([O:28][C:5]3[C:10]4[C:11]([C:2](=[O:1])[C:3](=[O:32])[C:4]=3[S:13][CH2:14]2)=[CH:6][CH:7]=[CH:8][CH:9]=4)[CH2:20][CH2:19]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 6422Trifluoroacetic acidHCID 57661963Tert-butyl 4-{[(3,4-dioxo-3,4-dihydronaphthalen-1-yl)thio]methyl}-4-hydroxypiperidine-1-carboxylate

Product 1

HCID 67438986Spiro[naphtho[1,2-b][1,4]oxathiine-2,4'-piperidinium]-5,6-dione chlorideYield 58%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 312751,4-DioxaneSolvent

Procedure

To a solution of tert-butyl 4-{[(3,4-dioxo-3,4-dihydronaphthalen-1-yl)thio]methyl}-4-hydroxypiperidine-1-carboxylate (3.8 g, 0.942 mmol) in 50 ml dichloromethane which was cooled to 0° C. was added trifluoroacetic acid (200 ml). The reaction mixture was stirred at room temperature for 30 hours and the solvent removed under reduced pressure. The mixture was dissolved in dichloromethane (150 ml) and poured over a 0° C. mixture of saturated sodium carbonate (500 ml) and water (200 ml). Methanol (500 ml) was then added to the reaction mixture and allowed to stir overnight. The mixture was extracted with dichloromethane (4×400 ml). The organic extracts were combined and washed with a mixture of 2.0M sodium carbonate and brine (5×500 ml). The organic layer was separated, dried with Na2SO4, and concentrated under reduced pressure to give a purple solid. To a stirred solution of the purple solid in dichloromethane (100 ml), 4.0 M HCl in dioxane (20 ml) was added dropwise. The precipitate was filtered, washed with dichloromethane and ether, and recrystallized from ethanol to give a purple crystalline solid (1.84 g, 58%). M.p.=229-232° C.; 400 MHz 1H NMR (DMSO-d6) δ: 9.19 (br. s, 2H), 7.90-7.86 (m, 1H), 7.84-7.80 (m, 1H), 7.76-7.71 (m, 1H), 7.58-7.53 (m, 1H), 3.33-3.25 (m, 2H), 3.16-3.07 (m, 4H), 2.22-2.15 (m, 2H), 2.20-1.50 (m, 2H); LCMS: 302 [M+H].

Workup

  1. customthe solvent removed under reduced pressure
  2. dissolutionThe mixture was dissolved in dichloromethane (150 ml)
  3. additionpoured over a 0° C.
  4. additionmixture of saturated sodium carbonate (500 ml) and water (200 ml)
  5. additionMethanol (500 ml) was then added to the reaction mixture
  6. stirringto stir overnight
  7. extractionThe mixture was extracted with dichloromethane (4×400 ml)
  8. washwashed with a mixture of 2.0M sodium carbonate and brine (5×500 ml)
  9. customThe organic layer was separated
  10. dry with materialdried with Na2SO4
  11. concentrationconcentrated under reduced pressure
  12. customto give a purple solid
  13. filtrationThe precipitate was filtered
  14. washwashed with dichloromethane and ether
  15. customrecrystallized from ethanol

Sources & evidence

ORD record
ord-a78c1cf2b4e247a887a3cbd494f68a5e
Source dataset
uspto-grants-2011_10
Patent number
US08039503B2

Reaction notes

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