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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.

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