Hydrochloric Acid → 1-azabicyclo[3.2.1]octan-6-one

Temperature

120 °C

A mixture of ethanol (9 ml) and toluene (10 ml) was added dropwise to a rapidly stirred suspension of potassium (6 g) in toluene (30 ml). at 120° C. After all the ethanol had been added the reaction mixture was stirred at 120° C. for 1 hr before adding a solution of 1-carboethoxymethyl-3-carboethoxy piperidine (15 g, 61.7 mmol) in toluene (40 ml) dropwise at 140° C. The reaction mixture was heated for 3 hr at 140° C. before adding concentrated hydrochloric acid (3×50 ml), and refluxing the aqueous phase for 16 hr. The solvent was removed in vacuo, water (100 ml) added and the solution neutralised with potassium carbonate. The solution was extracted with dichloromethane (3×150 ml, the combined extracts washed with saturated sodium chloride solution, dried (Na2SO4) and evaporated. The crude product was chromatographed through slicia-gel, eluting with dichloromethane/methanol (90:10) to give 1-azabicyclo[3:2:1]octan-6-one as a crystalline solid (1.1 g): mp. 83°-87° (hexane): m/e 125 (M+): δ(360 MHz, CDCl3) 1.30-2.40 (5H, m, 2×CH2, and CH): 3.12 (2H, s, CH2 --N); 2.60-3.60 (4H, m, 2×CH2 --N).

1. customat 120° C
2. temperatureThe reaction mixture was heated for 3 hr at 140° C.
3. temperaturerefluxing the aqueous phase for 16 hr
4. customThe solvent was removed in vacuo, water (100 ml)
5. additionadded
6. extractionThe solution was extracted with dichloromethane (3×150 ml
7. washthe combined extracts washed with saturated sodium chloride solution
8. dry with materialdried (Na2SO4)
9. customevaporated
10. customThe crude product was chromatographed through slicia-gel
11. washeluting with dichloromethane/methanol (90:10)
12. customto give 1-azabicyclo[3

ORD record

ord-a50c6ebd756f4e6982303972754ce214

Source dataset

uspto-grants-1997_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05686463