Reaction Steps
A suspension of the Boc-valine ester 74-A (151 mg, 0.195 mmol) and a solution of HCl (0.49 ml, 1.95 mmol, 4M in 1,4-dioxane) in anhydrous DCM (10 ml) was stirred at rt for 2.5 h. The reaction mixture was concentrated and diluted with a saturated aqueous solution of sodium bicarbonate. The aqueous solution was extracted with DCM containing traces of methanol. The combined organic layer was dried over anhydrous magnesium sulfate, filtered and concentrated. The residue was purified by Biotage (Silia Flash 12 g cartridge; 2% of ammonium hydroxide in MeOH/DCM: 1/99 to 15/85 over 20 CV, then 15/85 to 20/80 over 10 CV), to afford the desired product 80 (80 mg, 0.118 mmol, 60% yield) as an off-white sticky solid. 1H NMR (400 MHz, DMSO-d6) δ (ppm): mixture of rotamers, 8.73 (s, 1H), 8.58 (bd, J=1.4 Hz, 1H), 8.52 (d, J=5.3 Hz, 1H), 8.34 (s, 1H), 8.26 (dd, J=8.1, 0.7 Hz, 1H), 7.88 (dd, J=8.2, 2.2 Hz, 1H), 7.73 (dd, J=13.6, 2.4 Hz, 1H), 7.38 (t, J=9.0 Hz, 1H), 7.20 (dd, J=9.0, 1.4 Hz, 1H), 6.65 (dd, J=5.3, 0.8 Hz, 1H), 6.59 (bd, J=2.5 Hz, 1H), 4.84 (d, J=14.7 Hz, 1H), 4.77 (d, J=14.9 Hz, 1H), 3.63-3.58 (m, 2H), 3.50-3.37 (m, 4H), 3.20 (d, J=5.1 Hz, 1H), 2.59-2.51 (m, 1H), 2.47-2.33 (m, 4H), 2.00-1.60 (m, 3H), 0.92 (d, J=6.8 Hz, 3H), 0.86 (d, J=6.8 Hz, 3H), 0.72-0.58 (m, 2H), 0.50-0.36 (m, 2H). MS (m/z): 577.6 and 676.7 (M+H).
