| 82% |
With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In toluene; at 100℃; for 5h; |
As reported in Ji, J.; Li, T.;Bunnelle, W. H., Org. Lett. 2003, 5, (24), 4611-4614, f-butyl 1-piperazinecarboxylate (11.18 g, 60 mmol), sodium t-butoxide (8.64 g, 90 mmol), Pd2(dba)3 (1.10 g, 1.20 mmol), and XantPhos (2.08 g, 3.6 mmol) were added to a solution of <strong>[53939-30-3]5-bromo-2-chloropyridine</strong> (11.54 g, 60 mmol) in toluene (300 mL). The mixture was evacuated and purged with argon (3 cycles), then heated at 100 0C for 5 h. The reaction mixture was then cooled to room temperature, diluted with ethyl acetate (1200 mL) and washed with water (300 mL). The organic solution was concentrated under pressure, and the residue was purified by flash chromatography on silica gel eluting with 17% ethyl acetate in hexane to give compound 5 as a light yellow solid (14.56 g, 82%). 1H NMR (400 MHz, CDCl3) delta 8.02 (IH, s), 7.19 - 7.18 (2H, m), 3.59 (4H, dd, J = 12 Hz, J = 4 Hz), 3.14 (4H, dd, J = 12 Hz, J = 4 Hz), 1.49 (9H, s) ppm; LCMS-ESI (POS), M/Z, M+l: Found 298.1, Calculated 298.1. |
| 72% |
With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In toluene; at 100℃;Inert atmosphere; |
tert-Butyl 4-(6-chloropyridin-3-yl)piperazine-l-carboxylate (67) A 250 mL single- necked round bottom flask was charged with <strong>[53939-30-3]5-bromo-2-chloropyridine</strong> (11.4 g, 59.2 mmol), /ert-butyl 1-piperazinecarboxylate (11.0 g, 59.2 mmol), tris(dibenzylideneacetone)dipalladium (o) (0.542 g, 0.592 mmol), 9,9-dimethyl-4,5- bis(diphenylphosphino)xanthene (1.03 g, 1.78 mmol), and sodium /-butoxide (8.54 g, 88.9 mmol). The flask was subjected to 3 cycles of evacuation and back-filling with N2 before toluene (100 mL) was introduced under N2. The resulting mixture was stirred at 100 0C overnight. After cooling, the product was purified by combi-flash column chromatography (EtOAc/Hexanes) to give /ert-butyl 4-(6-chloropyridin-3-yl)piperazine- 1-carboxylate (66) (12.7 g, 72.0% yield) as an off-white solid. 1H NMR (500 MHz, DMSO-d6) delta ppm 8.08 (1 H, d, J=3.2 Hz), 7.43 (1 H, dd, J=8.8, 3.2 Hz), 7.31 (1 H, d, J=8.8 Hz), 3.42 - 3.49 (4 H, m), 3.14 - 3.21 (4 H, m), 1.42 (9 H, s). LCMS-ESI (POS), M/Z, M+l: Found 298.1 |
| 53% |
With sodium t-butanolate;tris-(dibenzylideneacetone)dipalladium(0); 4,5-bis(diphenylphos4,5-bis(diphenylphosphino)-9,9-dimethylxanthenephino)-9,9-dimethylxanthene; In toluene; at 20℃; for 4h;Heating / reflux; |
Intermediate 18; 4-(6-Chloropyridin-3-yl)pipcrazinc-l-carboxylic acid tert-butyl ester; A mixture of <strong>[53939-30-3]2-chloro-5-bromopyridine</strong> (1.Og, 5.2 mmol), 1-boc-piperazine (0.967g, 5.2 mmol), sodium tert-butoxide (0.749g, 7.8 mmol), 9,9-dimethyl-4,5- bis(diphenylphosphino)xanthene (0.179g, 0.31 mmol) in toluene (3OmL) was treated with Pd2(dba)3 (0.095g, 0.1 mmol) at rt. The mixture was refluxed for 4h. The reaction was cooled and filtered through celite. The organic layer was diluted with EtOAc (10OmL) then washed with saturated Na2CO3 solution, brine, dried (MgSO4) and the solvent removed in vacuo. The crude mixture was purified by flash chromatography with 20% EtOAc / Hexane as eluent to afford the title compound (0.82g, 53%): RT = 3.40 min; m/z (ES+) = 298.2 [M+ H]+ |
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