Reaction Steps
A solution of rac-BINAP (43.8 mg, 0.070 mmol) and Pd2(dba)3 (32.2 mg, 0.0352 mmol) in toluene (1 mL) was stirred under nitrogen atmosphere in a sealed vial at 90° C. for 10 min, then cooled to 40° C. and cannulated into a stirring solution of tert-butyl 4-ethyl-5-oxa-2,9-diazaspiro[5.5]undecane-9-carboxylate (500 mg, 1.76 mmol) and 2-chloropyridine (200 mg, 165 μL, 1.76 mmol) in toluene (6 mL). The solution was treated with sodium tert-butoxide (275 mg, 2.87 mmol), flushed with nitrogen and stirred for 3 h at 90° C. The reaction mixture was cooled, diluted with ethyl acetate (100 mL), filtered through Celite and concentrated in vacuo. Silica gel chromatography (120 g silica, 10-70% ethyl acetate/hexane) provided tert-butyl 10-ethyl-8-(2-pyridyl)-11-oxa-3,8-diazaspiro[5.5]undecane-3-carboxylate (486 mg, 1.34 mmol, 76%) as an orange-colored oil. ESI-MS m/z calc. 361.2. found 362.3 (M+1)+; Retention time: 1.25 minutes (3 min run). 1H NMR (400 MHz, DMSO-d6) δ 8.08 (dd, J=4.9, 1.4 Hz, 1H), 7.51 (ddd, J=8.8, 7.1, 2.0 Hz, 1H), 6.85 (d, J=8.7 Hz, 1H), 6.61 (dd, J=6.7, 4.9 Hz, 1H), 4.24 (d, J=12.0 Hz, 1H), 4.11 (d, J=12.9 Hz, 1H), 3.75-3.51 (m, 3H), 3.15 (br s, 1H), 2.91 (br s, 1H), 2.59 (d, J=13.0 Hz, 1H), 2.40 (dd, J=12.6, 10.9 Hz, 1H), 2.02 (d, J=13.3 Hz, 1H), 1.60-1.42 (m, 4H), 1.39 (s, 9H), 1.36-1.26 (m, 1H), 0.95 (t, J=7.5 Hz, 3H).
