Reaction Steps
A solution of alcohol 2 (385 mg, 1.0 mmol) in CH2Cl2 (3 mL) was treated with (2S)-1-(1,2-dioxo-3,3-dimethylpentyl)-2-piperidinecarboxylic acid (23, 255 mg, 1.0 mmol, prepared from L-pipercolic acid in 4 steps following literature procedures by Holt et al. J. Amer. Chem. Soc., 1993, 115, 9925-9938), followed by 1,3-dicyclohexylcarbodiimide (DCC, 247 mg, 1.2 mmol), and 4-(dimethylamino)-pyridine (DMAP, 85 mg, 0.70 mmol) under a nitrogen atmosphere. The resulting bright yellow suspension was allowed to stir overnight. The mixture was then filtered through glass wool and chromatographed (silica gel, 20% EtOAc/hexanes) to give (1R)-3-Phenyl-1-[3-9(3-tert-butyloxycarbamoylpropyl)oxy)phenyl]-1-propyl (2S)-1-(3,3-dimethyl-1,2-dioxopentyl)-2-piperidinecarboxylate (524 mg, 84%) as a colorless oil: 1H NMR (CDCl3, 300 MHz) (single diastereomer, mixture of rotamers) 7.35-6.90 (m, 9H), 5.80 (t, J=5.9 Hz, 1H), 5.32 (d, J=5.0 Hz, 0.82 H, pipercolate a-H of rotamer A), 4.80 (br. s, 1H), 4.02 (t, J=6.1 Hz, 2H), 3.40-3.25 (m, 3H), 3.12 (td, J=13.0, 3.3 Hz, 1H), 2.60 (m, 2H), 2.35 (d, J=14 Hz, 1H), 2.28 (m, 1H), 2.07 (m, 1H), 1.96 (t, J=6.3 Hz, 2H), 1.80-1.60 (m, 5H), 1.43 (s, 9H), 1.22 (s, 3H), 1.20 (s, 3H), 0.88 (t, J=7.4 Hz, 3H); 13C NMR (CDCl3, 75 MHz) (single diastereomer, mixture of rotamers) 208.2, 170.1, 167.6, 159.4, 156.4, 141.7, 141.3, 130.1, 128.9, 128.7, 1265, 119.4, 114.7, 113.2, 113.0, 66.1, 57.1, 51.7, 47.1, 44.5, 38.3, 32.9, 32.1, 30.0, 28.8, 26.8, 25.4, 24.9, 24.0, 23.8, 23.5, 21.6, 9.1. MS(FAB): (M+Na)+ 645, (M+H)+ 623.
