Tris(1,1-dimethylethyl)phosphine → 1,1-Dimethylethyl 4-(6-amino-3,4-dihydro-1(2H)-quinolinyl)-1-piperidinecarboxylate

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Reaction Steps

A suspension of Pd2(dba)3 (29 mg, 0.032 mmol) in 2 mL anhydrous THF was treated with PtBu3 (400 μL of a 10% wt in hexanes solution, 0.13 mmol) and stirred at room temperature for 5 minutes. To this mixture was added tert-butyl 4-(6-bromo-3,4-dihydroquinolin-1(2H)-yl)piperidine-1-carboxylate (250 mg, 0.63 mmol) followed by lithium hexamethyldisilizane (1.3 mL of a 1 M solution in THF, 1.3 mmol). The resulting dark brown suspension was heated at 95° C. for 3 hours. The mixture was cooled to room temperature and treated with 5 ml of a 1M tetrabutylammonium fluoride solution in THF then stirred at room temperature for 30 minutes. The mixture was partitioned between ethyl acetate (100 mL) and H2O (20 mL). After extraction, the organic layer was separated, dried over Na2SO4, filtered and concentrated to give a dark brown residue. This residue was subjected to flash chromatography on silica gel using 2.5% 2M NH3 in methanol/CH2Cl2 to give a viscous dark brown residue (160 mg, 76.6%). 1H-NMR (CDCl3) δ 6.56 (d, J=8.4 Hz, 1H), 6.48 (dd, J=2.7, 8.7 Hz, 1H), 6.43-6.42 (m, 1H), 4.25-4.21 (m, 2H), 3.69-3.59 (m, 1H), 3.24 (br s, 2H), 3.07 (t, J=5.4 Hz, 2H), 2.78-2.72 (m, 2H), 2.66 (t, J=6.6 Hz, 2H), 1.93-1.83 (m, 2H), 1.76-1.55 (m, 4H), 1.47 (s, 9H). MS (ESI): 332.2 (M+1, 100%).

Provenance & Evidence