Reaction Steps
Example 4 was prepared from 3-(2-(benzyloxymethyl)-2H-tetrazol-5-yl)-N—((R)-4-((S)-4-(4-chlorophenyl)-4-hydroxy-3,3-dimethylpiperidin-1-yl)-4-oxobutan-2-yl)benzamide using the conditions described in Example 2. MS (ESI+)=497.2 (M+H)+. 1H NMR (CD3OD, 500 MHz) (NMR shows several rotamers) δ ppm 8.55 (s, 0.6 H), 8.49 (s, 0.4 H), 8.23 (d, J=7.8 Hz, 0.6 H), 8.20 (d, J=7.8 Hz, 0.4 H), 8.05 (d, J=8.2 Hz, 0.6 H), 8.00 (d, J=7.8 Hz, 0.4 H), 7.75-7.66 (m, 1 H), 7.47 (d, J=8.7 Hz, 0.9 H), 7.36-7.28 (m, 2.1 H), 7.22 (d, J=8.7 Hz, 1 H), 4.64-4.48 (m, 1.4 H), 4.11 (dt, J=13.3, 2.5 Hz, 0.6 H), 4.05 (dd, J=12.8, 1.8 Hz, 0.6 H), 3.69-3.54 (m, 1.4 H), 3.13 (td, J=12.9, 3.4 Hz, 0.6 H), 3.10-3.03 (m, 1 H), 2.98 (dd, J=15.1, 6.0 Hz, 0.4 H), 2.70-2.56 (m, 1.6 H), 2.53 (dd, J=15.1, 7.3 Hz, 0.4 H), 1.58-1.48 (m, 1 H), 1.42 (d, J=6.9 Hz, 1.8 H), 1.36 (d, J=6.4 Hz, 1.2 H), 1.35-1.26 (m, 0.6 H), 0.90 (t, J=6.9 Hz, 0.4 H), 0.84 (s, 1.2 H), 0.84 (s, 1.2 H), 0.77 (s, 1.8 H), 0.69 (s, 1.8 H); HPLC Method: Inj. Vol.=5 uL; Start % B=10, 12 Min. 100%, 15 Min. 100%, Flow Rate=1 ml/min, Wavelength 1=220, Wavelength 2=254, Solvent A=0.05% TFA in H2O:MeCN (95:5), Solvent B=0.05% TFA in H2O:MeCN (5:95), Col-1: Sunfire C18 3.5 um, 4.6×150 mm; Retention Time=11.08 min., Col-2: Xbridge Phenyl 3.5 um, 4.6×150 mm; Retention Time=10.57 min.
