Reaction Steps
A solution of (S)-(+)-Hiva (3, 1.00 g, 8.5 mmol), 2-aminobenzothiazole (6q, 1.27 g, 8.5 mmol) and HOBt (2.29 g, 17 mmol, 2 eq) in dry THF (15 ml) is cooled to 0° C., under N2, with stirring. To the solution is added NMM (0.93 mL, 8.5 mmol) and a solution of DCC (1.75 g, 8.5 mmol) in THF (5 mL). The reaction is then allowed to reach room temperature over 2 hours. The solution is filtered and concentrated to dryness. The oily residue is dissolved in CH2Cl2 (50 mL) and washed successively with saturated NaHCO3 solution (50 mL), H2O (50 mL), 10% citric acid solution (50 mL), and H2O (2×50 mL). The organic extract is then dried and the solvent evaporated under reduced pressure to give a crude white solid. Urea by-product is removed by repeated precipitations from ice-cold EtOAc, and the product is recrystallized (three times) from acetone-heptane to give the pure amide as colorless microcrystalline needles (1.8 g, 85%). mp 184.1-184.2° C.; Rf 0.59 (CH2Cl2-EtOAc, 4:1); [α]24D −69.3° (c=1.0); MS m/z 250 (9, M+), 151 (14), 150 (100), 123 (8), 96 (7), 82 (21), 80 (21), 73 (6), 55 (13); 1H NMR (300 MHz, CDCl3) δ 0.97 (d, J=6.9 Hz, 3H, Val CH3), 1.23 (d, J=6.9 Hz, 3H, Val CH3), 2.45 (spd, J1=6.9 Hz, J2=3.0 Hz, 1H, Hiva CHβ), 4.41 (bt, J=3.0 Hz, 1H, Hiva CHα), 5.00 (bd, J=3.9 Hz, 1H, OH), 7.35 (t, J=8.4 Hz, 1H, ArH), 7.47 (t, J=8.4 Hz, 1H, ArH), 7.76 (d, J=8.4 Hz, 1H, ArH), 7.85 (d, J=7.5 Hz, 1H, ArH), 10.55 (bs, 1H, NH). Anal. Calcd. For C12H14N2O2S: C, 57.78; H, 5.64; N, 11.9. Found: C, 57.90; H, 5.87; N, 10.89.
