1,1-Ethanediol → (cis)-spiro[1,3-dioxolane-2,6'-2,4,4a,5,7,7a-hexahydro-1H-cyclopenta[c]pyridine]-3'-one

HRID 2364694Notes

Reaction equation

HRID 2364694 reaction equation
[CH2:1]1[C@H:6]2[CH2:7][C:8](=[O:10])[CH2:9][C@H:5]2[CH2:4][C:3](=[O:11])[NH:2]1.[CH:12](O)([OH:14])[CH3:13].C(=O)(O)[O-].[Na+]>C1(C)C=CC=CC=1.C1(C)C=CC(S(O)(=O)=O)=CC=1>[CH2:1]1[C@H:6]2[CH2:7][C:8]3([O:14][CH2:12][CH2:13][O:10]3)[CH2:9][C@H:5]2[CH2:4][C:3](=[O:11])[NH:2]1

Participants

6

Reactant 3

HCID 1512111,1-EthanediolHCID 516892Sodium BicarbonateHCID 11030030rac-(4aR,7aR)-octahydro-1H-cyclopenta[c]pyridine-3,6-dione

Product 1

HCID 68242997(cis)-spiro[1,3-dioxolane-2,6'-2,4,4a,5,7,7a-hexahydro-1H-cyclopenta[c]pyridine]-3'-oneYield 71.5%

Reagents, catalysts & solvents 2

HCID 6101p-Toluenesulfonic acidCatalystHCID 1140TolueneSolvent

Procedure

(cis)-2,4,4a,5,7,7a-hexahydro-1H-cyclopenta[c]pyridine-3,6-dione 14d (1.20 g, 7.80 mmol), ethanediol (1.34 g, 21.50 mmol) and p-toluenesulfonic acid (24 mg, 0.13 mmol) were dissolved in 60 mL of toluene, heated to reflux for 8 hours with stirring, then added dropwise with saturated sodium bicarbonate solution to adjust pH to 7 around and extracted with dichloromethane (50 mL). The aqueous phase was extracted with dichloromethane (50 mL×3). The combined organic phase was washed with saturated sodium chloride solution (50 mL×3), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound (cis)-spiro[1,3-dioxolane-2,6′-2,4,4a,5,7,7a-hexahydro-1H-cyclopenta[c]pyridine]-3′-one 14e (1.10 g, yield: 70.0%) as a white solid.

Workup

  1. temperatureheated
  2. temperatureto reflux for 8 hours
  3. extractionextracted with dichloromethane (50 mL)
  4. extractionThe aqueous phase was extracted with dichloromethane (50 mL×3)
  5. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL×3)
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe resulting residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-7943b96a96674cc9ad94359d433528fc
Source dataset
uspto-grants-2014_04
Patent number
US08691822B2

Reaction notes

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