Carbamate → HCID 12085276, compound

To a solution of 186 mg of the above tert-butyl carbamate (0.55 mmol, 1 equiv.) in 1.6 mL anhydrous tert-butanol was added 52 μL of pyridine-3-carboxaldehyde (0.55 mmol, 1 equiv.) and 1.65 mL potassium tert-butoxide solution (1.0 M, 1.32 mmol, 3 equiv.). The mixture was heated to reflux overnight, then cooled. MeOH (5 mL) and HCl solution in dioxane (4.0 M) were added until pH 1, the reaction was then stirred for 1.5 h at ambient temperature. The mixture was then quenched with saturated NaHCO3 aqueous solution and extracted with EtOAc (2×50 mL). The aqueous layer was treated with 4 N NaOH aqueous solution until pH˜12 and extracted 2 more times. The combined organic extracts were washed with brine, dried (MgSO4), filtered and concentrated to afford a mixture of crude products, including naphthylamine still protected as the carbamate. The residue was therefore taken up in dichloromethane (3 mL), treated with 2 mL TFA and left stirring over a weekend at ambient temperature. The mixture was quenched and neutralized with saturated aqueous NaHCO3, extracted with dichloromethane (3×50 mL), dried (MgSO4) and filtered. The volatiles were removed in vacuo and the crude product purified by column chromatography on SiO2 using 50 to 100% EtOAc in hexane eluent mixtures giving 35 mg (0.11 mmol, 20% of theoretical yield) title compound.

1. temperatureThe mixture was heated
2. temperatureto reflux overnight
3. temperaturecooled
4. customThe mixture was then quenched with saturated NaHCO3 aqueous solution
5. extractionextracted with EtOAc (2×50 mL)
6. additionThe aqueous layer was treated with 4 N NaOH aqueous solution until pH˜12
7. extractionextracted 2 more times
8. washThe combined organic extracts were washed with brine
9. dry with materialdried (MgSO4)
10. filtrationfiltered
11. concentrationconcentrated
12. customto afford
13. additiona mixture of crude products
14. waitleft
15. stirringstirring over a weekend at ambient temperature
16. customThe mixture was quenched
17. extractionextracted with dichloromethane (3×50 mL)
18. dry with materialdried (MgSO4)
19. filtrationfiltered
20. customThe volatiles were removed in vacuo
21. customthe crude product purified by column chromatography on SiO2 using 50 to 100% EtOAc in hexane eluent mixtures
22. customgiving

ORD record

ord-e7d08fe8114c4f338f02a5bd72b3a94e

Source dataset

uspto-grants-2003_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06608052B2