Hydrochloric Acid → HCID 131718773, compound

Temperature

-30 °C

A solution of (±) ethyl 1-azabicyclo[3.2.1]-oct-3-en-3-ylcarboxylate (D6) (0.52 g, 2.9 mmole) in ethanol (6 ml) was treated with 85% potassium hydroxide (0.38 g, 5.7 mmole) then heated under reflux for 9h. The reaction mixture was concentrated in vacuo, treated with 5N hydrochloric acid (1.72 ml, 8.6 mole) then concentrated in vacuo and co-distilled with toluene to remove the last traces of water. The residue was treated with thionyl chloride (10 ml), heated at reflux under nitrogen for 25 minutes then concentrated in vacuo and co-distilled with toluene to afford the crude acid chloride. A solution of this material in a mixture of dry acetonitrile (12 ml) and dry chloroform (10 ml), under nitrogen, was treated with methoxylamine hydrochloride (0.48 g, 5.8 mmole) then cooled to -30° C. and treated in a single rapid addition with pyridine (1.09 g, 29 mmole) in acetonitrile (2 ml). The reaction mixture was allowed to warm to room temperature and stirred at room temperature overnight. It was then treated with saturated aqueous potassium carbonate (25 ml), the organic phase was separated, and the aqueous phase extracted with chloroform (8×25 ml). The combined organic extracts were dried (Na2SO4), concentrated in vacuo and the residue chromatographed on neutral alumina in a gradient of 0-10% methanol in chloroform to afford the title compound (D7) as a brown gum (0.17 g, 34%).

1. temperaturethen heated
2. temperatureunder reflux for 9h
3. concentrationThe reaction mixture was concentrated in vacuo
4. concentrationthen concentrated in vacuo and co-distilled with toluene
5. customto remove the last traces of water
6. additionThe residue was treated with thionyl chloride (10 ml)
7. temperatureheated
8. temperatureat reflux under nitrogen for 25 minutes
9. concentrationthen concentrated in vacuo and co-distilled with toluene
10. customto afford the crude acid chloride
11. temperatureto warm to room temperature
12. customthe organic phase was separated
13. extractionthe aqueous phase extracted with chloroform (8×25 ml)
14. dry with materialThe combined organic extracts were dried (Na2SO4)
15. concentrationconcentrated in vacuo
16. customthe residue chromatographed on neutral alumina in a gradient of 0-10% methanol in chloroform

ORD record

ord-2baa5eec5533458bb1d6b5948a7e0185

Source dataset

uspto-grants-1994_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05362739