Sodium Hydroxide → 5,6,7,8,9,10-Hexahydro-6,9-methanocycloocta[b]pyridin-11-one

HRID 902441Notes

Reaction equation

HRID 902441 reaction equation
C(N(C(C)C)CC)(C)C.N1([C:15]2[CH2:19][CH2:18][CH2:17][CH:16]=2)CCCC1.Cl[CH2:21][C:22]1[C:27]([CH2:28]Cl)=[CH:26][CH:25]=[CH:24][N:23]=1.[OH-:30].[Na+]>C(#N)C>[N:23]1[CH:24]=[CH:25][CH:26]=[C:27]2[CH2:28][CH:15]3[C:16](=[O:30])[CH:17]([CH2:21][C:22]=12)[CH2:18][CH2:19]3

Participants

6

Reactant 4

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 81570Pyrrolidine, 1-(1-cyclopenten-1-yl)-HCID 145187502,3-Bis(chloromethyl)pyridine

Product 1

HCID 724081745,6,7,8,9,10-Hexahydro-6,9-methanocycloocta[b]pyridin-11-one

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
0 °C

Procedure

Diisopropylethylamine (6.6 mL, 38 mmol) and 1-pyrrolidinocyclopentene (2.8 mL, 19 mmol) were added to a stirred solution of freshly prepared 2,3-bis(chloromethyl)pyridine [K. Tsuda et al; Pharm. Bull. 1, 1953, 142 ] (2.6 g, 15 mmol) in dry acetonitrile (50 mL) at 0° C. under nitrogen. The reaction was stirred for 15 minutes at this temperature, then 1 hour at room temperature. The mixture was then stirred and heated at reflux for 2 hours. The reaction was allowed to cool, the volatiles removed in vacuo, and the residue taken up in water (40 mL). Concentrated hydrochloric acid was added to give pH 1, and the mixture heated at reflux for 24 hours. The reaction was cooled to 0° C. and basified with 4N aqueous sodium hydroxide, and the dark mixture extracted with dichloromethane (×4). The combined extracts were dried (Na2SO4), filtered and evaporated, and the residue purified by chromatography on silica gel, eluting with 80% ethyl acetate/hexanes to 100% ethyl acetate to give (6S/R,9R/S)-5,6,7,8,9,10-hexahydro-6,9-methanocycloocta[b]pyridin-11-one (700 mg) as a dark oil (˜75% pure); MS (ES+) 188 ([MH]+). This material was used without further purification.

Workup

  1. custom1 hour
  2. customat room temperature
  3. stirringThe mixture was then stirred
  4. temperatureheated
  5. temperatureat reflux for 2 hours
  6. temperatureto cool
  7. customthe volatiles removed in vacuo
  8. additionConcentrated hydrochloric acid was added
  9. customto give pH 1
  10. temperaturethe mixture heated
  11. temperatureat reflux for 24 hours
  12. extractionthe dark mixture extracted with dichloromethane (×4)
  13. dry with materialThe combined extracts were dried (Na2SO4)
  14. filtrationfiltered
  15. customevaporated
  16. customthe residue purified by chromatography on silica gel
  17. washeluting with 80% ethyl acetate/hexanes to 100% ethyl acetate

Sources & evidence

ORD record
ord-ebc95ac2657642f4888419247a565294
Source dataset
uspto-grants-2008_04
Patent number
US07365196B2

Reaction notes

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