Hydrochloric Acid → Tert-butyl 4-(4-(ethoxycarbonyl)-2-oxo-2,3-dihydroimidazol-1-yl)piperidine-1-carboxylate

4-Amino-1-Boc-piperidine (1.60 g, 7.99 mmol) was dissolved in a mixture of dichloromethane (30 mL) and aqueous sodium bicarbonate (15 mL). 20% Phosgene in toluene (4.8 mL, 9.12 mmol) was added to the mixture in one portion with vigorous stirring. Reaction stirred vigorously at room temperature for 15 minutes. A solution of ethyl 2-amino-3,3-diethoxypropanoate (1.95 g, 9.50 mmol) in 20 mL dichloromethane was added to the mixture. Reaction stirred vigorously at room temperature for 30 minutes. Reaction layers were partitioned and the aqueous phase was back extracted with dichloromethane. Organic layers were combined. Material was washed twice with 1N hydrochloric acid and the aqueous phase was discarded. Material was washed with brine and the aqueous phase was discarded. Organics were dried MgSO4, filtered and then concentrated to dryness. 2.70 g (6.26 mmol) of the residue was suspended in water (25 ml). Concentrated hydrochloric acid (25 ml, 304 mmol) was added to the mixture. Reaction was warmed to 80° C. and held with stirring for 5 minutes. Mixture was cooled to room temperature. Reaction mixture was carefully poured into a stirred solution of sodium carbonate (16.19 g, 153 mmol) in 50 mL water. 1,4-Dioxane (50 ml) was added to the mixture followed by di-tert-butyl dicarbonate (1.60 g, 7.33 mmol). Reaction stirred at room temperature for 2 hours. Mixture was extracted twice with ethyl acetate and the aqueous phase was discarded. Organics were dried MgSO4, filtered and then concentrated to dryness. Silica gel chromatography eluting ethyl acetate-hexanes afforded the title compound as tan foam in 19% yield. MS (M−H)−=338.2.

1. customReaction
2. customReaction
3. stirringstirred vigorously at room temperature for 30 minutes
4. customReaction layers
5. customwere partitioned
6. extractionthe aqueous phase was back extracted with dichloromethane
7. washMaterial was washed twice with 1N hydrochloric acid
8. washMaterial was washed with brine
9. filtrationfiltered
10. concentrationconcentrated to dryness
11. customReaction
12. temperaturewas warmed to 80° C.
13. stirringwith stirring for 5 minutes
14. temperatureMixture was cooled to room temperature
15. customReaction mixture
16. customReaction
17. stirringstirred at room temperature for 2 hours
18. extractionMixture was extracted twice with ethyl acetate
19. filtrationfiltered
20. concentrationconcentrated to dryness
21. washSilica gel chromatography eluting ethyl acetate-hexanes

ORD record

ord-4178e9aba42d42d69bcf51746f21ea92

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07470680B2