Reaction Steps
To a solution of CBZ-L-His(CBZ)-OH (0.136 g, 0.32 mmol) and N-ethyl morpholine (32 L, 0.25 mmol) in THF (1 mL) and DMF (0.1 mL) at −18° C. was added i-butyl chloroformate (42 L, 0.32 mmol). After an activation period of 10 min a solution of 7 (0.100 g, 0.25 mmol) and N-ethyl morpoholine (42 L, 0.33 mmol) in THF (1 mL) was added dropwise. The reaction mixture was stirred under nitrogen at −18° C. for 1 h then overnight at room temperature. The reaction mixture was cooled to 0° C. followed by addition of NaHCO3 (1 mL, 5% aqueous solution). After 10 min this solution was warmed to room temperature and diluted with EtOAc (5 mL). The aqueous layer was removed and washed 1 with 5 mL EtOAc. The organics were combined and washed 3 with 10 mL 1 N HCl, dried over Na2SO4 and concentrated. The residue was purified by flash column chromatography (70% EtOAc/haxanes) to provide 8 as a white solid (0.159 g, 91%). mp=62-64° C.; 1H NMR (CDCl3) 8.08 (br s, 1H), 7.94 (br s, 1H), 7.43 (m, 6H), 7.31 (m, 12H), 7.10 (m, 2H), 7.01 (m, 1H), 6.79 (br s, 1H), 6.45 (br d, J=6.6 Hz, 1H), 5.34 (d, J=12.0 Hz, 1H), 5.31 (d, J=12.0 Hz, 1H), 4.88-5.11 (m, 5H), 4.60 (br s, 1H), 3.23 (br m, 2H), 3.00 (dd, J=14.8, 5.2 Hz, 1H), 2.92 (dd, J=14.8, 5.2 Hz, 1H) ppm; 13C NMR (CDCl3) 171.3, 170.6, 156.14, 147.9, 138.3, 136.5, 136.3, 135.9, 135.2, 133.7, 129.2, 128.8, 128.7, 128.6, 128.5, 128.4, 128.3, 128.2, 128.1, 127.3, 123.3, 121.9, 119.4, 118.4, 114.9, 111.1, 109.2, 70.0, 67.0, 66.9, 54.5, 52.6, 29.7, 27.4 ppm; IR (KBr) 3347, 3034, 2927, 1752, 1734, 1670, 1405, 1247, 1012, 742, cm−1; HRMS submitted.
