Water → HCID 25192131, compound

10% Pd/C (0.25 g) was added to a solution of 2-azabicyclo[2.2.1]hept-5-en-3-one in THF (30 ml) and dichloromethane (30 ml) and the mixture hydrogenated at room temperature for 18 h. The solids were filtered off, the solvent evaporated under vacuum, the residue dissolved in THF (60 ml) and lithium aluminum hydride (2 g) added slowly. The mixture was refluxed for 1 h and cooled to +5° C. before adding hexane (60 ml) and concentrated sodium hydroxide solution (4 ml). Celite (2 g) was added and the mixture stirred for 1 h before filtering off the solids and washing with THF (10 ml). To the mixture was added triethylamine (3 ml) and a solution of [2,1,3]-benzoxadiazole-5-carbonylchloride (2 g, 11.0 mmol) in dichloromethane (10 ml) and the mixture stirred overnight. Water (100 ml) was added, acidified to pH 2 with sulfuric acid and extracted with ethyl acetate (2×100 ml). The combined organics were washed with saturated sodium bicarbonate solution (100 ml), dried (NaSO4) and evaporated onto silica gel (5 g) and the residue was chromatographed on silica gel eluting with ethyl acetate/hexane (1:1)→(3:1)→(1:0) to give the desired product as white crystals (0.28 g) after crystallization from MTBE/hexane: mp=92-93° C., LC-MS, MH+=244; 1H NMR (300 MHz, CDCl3, rotamers) δ 7.93-7.87 (m, 2H), 7.59-7.54 (m, 1H), 4.79 and 4.17 (s, total 1H), 3.61 and 3.48 (m, total 1H), 3.28 and 3.08 (dd, J=9.3 and 1.5 Hz, total 1H), 2.74 and 2.64 (s, total 1H), 1.90-1.47 ppm (m, 6H).

1. filtrationThe solids were filtered off
2. customthe solvent evaporated under vacuum
3. dissolutionthe residue dissolved in THF (60 ml)
4. additionlithium aluminum hydride (2 g) added slowly
5. temperatureThe mixture was refluxed for 1 h
6. temperaturecooled to +5° C.
7. additionbefore adding hexane (60 ml) and concentrated sodium hydroxide solution (4 ml)
8. additionCelite (2 g) was added
9. filtrationbefore filtering off the solids
10. washwashing with THF (10 ml)
11. additionTo the mixture was added triethylamine (3 ml)
12. extractionextracted with ethyl acetate (2×100 ml)
13. washThe combined organics were washed with saturated sodium bicarbonate solution (100 ml)
14. dry with materialdried (NaSO4)
15. customevaporated onto silica gel (5 g)
16. customthe residue was chromatographed on silica gel eluting with ethyl acetate/hexane (1:1)→(3:1)→(1:0)

ORD record

ord-b9f7cb526f7f4c5ba1bcffde53464b31

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08110584B2