反应详情

1-Azabicyclo[3.3.1]non-5-ylcarboxylic acid hydrochloride salt (D14) (1.79 g, 0.0087 mole) was treated with thionyl chloride (20 ml) and heated under reflux for 5 h. The solution was concentrated in vacuo to leave a white solid, which was taken up in chloroform (150 ml), treated with acetamide oxime (D17) (770mg, 0.0104 mole) and heated under reflux for 6 h. The reaction mixture was basified with saturated potassium carbonate solution and extracted with chloroform (3×80 ml). The combined extracts were dried (Na2SO4) and concentrated to leave a white solid, which was treated with xylene (200 ml) and heated under reflux for 1.5 h, using a Dean and Stark head to trap water formed. The reaction mixture was concentrated in vacuo to leave a yellow oil, which was chromatographed on silica gel eluting with 5% methanol/chloroform to give a colourless oil (1.60 g, 89%). This was converted to the oxalate salt and recrystallised from ethanol/ether to give the title compound (E9) as a white solid m.p. 168°-170° C.

1. temperatureheated
2. temperatureunder reflux for 5 h
3. concentrationThe solution was concentrated in vacuo
4. customto leave a white solid, which
5. temperatureheated
6. temperatureunder reflux for 6 h
7. extractionextracted with chloroform (3×80 ml)
8. dry with materialThe combined extracts were dried (Na2SO4)
9. concentrationconcentrated
10. customto leave a white solid, which
11. temperatureheated
12. temperatureunder reflux for 1.5 h
13. customformed
14. concentrationThe reaction mixture was concentrated in vacuo
15. customto leave a yellow oil, which
16. customwas chromatographed on silica gel eluting with 5% methanol/chloroform