Formic Acid → 3-(4-Fluoro-phenyl)-3,4,9-triaza-tricyclo[5.3.1.02,6]undeca-2(6),4-diene

To a solution of 9-benzyl-3-(4-fluoro-phenyl)-3,4,9-triaza-tricyclo[5.3.1.020.6]undeca-2(6),4-diene (0.23 mmol) in methanol (2 ml) was added a solution of 1N HCl in diethyl ether (2 mL). The mixture was stirred for 45 min. and the solvent was removed to yield a solid. In a separate flask piperdine (1.5 mmol) and formic acid (0.69 mmol) were combined in methanol (2 ml). To this solution is added a solution of the HCl salt of 9-benzyl-3-(4-fluoro-phenyl)-3,4,9-triaza-tricyclo[5.3.1.02,6]undeca-2(6),4-diene in methanol (3 ml). To this resulting solution was added Pearlman's catalyst (8 mg, 10% wt. on carbon). The reaction mixture was heated under reflux under a nitrogen atmosphere for 18 h then it was cooled and filtered through a plug of Celite™ to remove solids and the pad was washed with methanol. The resulting filtrate was condensed to a gum, which is taken up in ethyl acetate and saturated aqueous sodium bicarbonate solution (20 ml). The mixture was extracted with ethyl acetate (3×20 mL) and the resulting organic layer was dried over MgSO4. The solids were removed by vacuum filtration and the solvent was removed to provide an oil which was purified by chromatography on silica gel eluting with 0.1% ammonium hydroxide solution in 10% methanol/dichloromethane to produce an oil that was treated with 1N HCl in ethyl ether. Trituration of the solids produced a gummy solid (0.082 mmol). 1H NMR (CD3OD, 400 MHz) δ 7.60 (m, 2H), 7.40 (s, 1H), 7.20 (br, 2H), 3.25 (m, 1H), 2.90–2.60 (m, 5H), 2.20 (m, 1H), 0.80 (br s, 1H); APCl MS m/z 244.2 (M+H)+.

1. customthe solvent was removed
2. customto yield a solid
3. temperatureThe reaction mixture was heated
4. temperatureunder reflux under a nitrogen atmosphere for 18 h
5. temperatureit was cooled
6. filtrationfiltered through a plug of Celite™
7. customto remove solids
8. washthe pad was washed with methanol
9. customcondensed to a gum, which
10. extractionThe mixture was extracted with ethyl acetate (3×20 mL)
11. dry with materialthe resulting organic layer was dried over MgSO4
12. customThe solids were removed by vacuum filtration
13. customthe solvent was removed
14. customto provide an oil which
15. customwas purified by chromatography on silica gel eluting with 0.1% ammonium hydroxide solution in 10% methanol/dichloromethane
16. customto produce an oil that

ORD record

ord-a5abd9af65b949ac829f4b7546008ebe

Source dataset

uspto-grants-2008_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07456177B2