Hydrochloric Acid → (6R,9aS)-8-Hydroxyhexahydro-2H-2,6-methanoquinolizin-3(4H)-one

Temperature

100 °C

A solution of 34 g of the tetrahydropyranyl ether of 7-ethoxycarbonyl-9-(ethoxycarbonylmethyl)-9-azabicyclo[3.3.1]nonan-3-ol in 800 ml of anhydrous toluene was treated with 19 g of potassium tert-butoxide and the stirred mixture heated at 100° C. for 2 hours. Anhydrous formic acid (7.85 g) was added to the cooled mixture, the potassium formate was filtered off, and the toluene solution evaporated to give a syrup. The syrup was treated with 300 ml of 5 N hydrochloric acid and the stirred solution refluxed overnight. The cooled mixture was clarified by an extraction with methylene chloride and the aqueous acid solution evaporated to dryness. The residue was dissolved in a little water and the solution treated with a large excess of saturated potassium carbonate solution. Extraction of the resulting mixture with ethyl acetate and evaporation of the dried ethyl acetate solution gave endo-hexahydro-8-hydroxy-2,6-methano-2H-quinolizin-3(4H)-one as an oil which crystallized on standing. The base was converted to its camphorsulfonate salt, m.p. 178° C., using one equivalent of camphorsulfonic acid in ethanol.

1. filtrationthe potassium formate was filtered off
2. customthe toluene solution evaporated
3. customto give a syrup
4. temperaturethe stirred solution refluxed overnight
5. extractionThe cooled mixture was clarified by an extraction with methylene chloride
6. customthe aqueous acid solution evaporated to dryness
7. dissolutionThe residue was dissolved in a little water
8. additionthe solution treated with a large excess of saturated potassium carbonate solution
9. extractionExtraction of the resulting mixture
10. customwith ethyl acetate and evaporation of the dried ethyl acetate solution

ORD record

ord-9135489007a34b8598e33a24911ac74e

Source dataset

uspto-grants-1990_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US04906755