Reaction Steps
To a solution of preparation 16 (97 mg, 0.20 mmol) in 2 mL of THF at −78° C. add methyl lithium (0.062 mL of a 1.6 M solution in Et2O, 0.10 mmol) followed by n-butyllithium (0.25 mL of a 1.6 M solution in hexanes, 0.40 mmol). Stir the solution for 15 min and then add DMF (0.077 mL, 1.0 mmol). Stir the solution for 30 min and then quench the reaction with saturated aqueous ammonium chloride. Let the solution warm to room temperature, separate; and back extract the aqueous solution with EtOAc. Wash the combined organic solutions with ½ brine, brine, dry over Na2SO4, filter and concentrate. Dissolve the material in 1 mL of THF and 1 mL of methanol. Add sodium borohydride (35 mg, 0.93 mmol). Let the solution stir for 30 min and quench the reaction with saturated aqueous ammonium chloride. Dilute the solution with EtOAc, wash with brine, dry over Na2SO4, filter and concentrate. Adsorb the material to silica gel and purify by silica gel flash chromatography (10 g, 0-30% A/B, A=EtOAc, B=10% CH2Cl2 in hexanes) to afford 68 mg (0.16 mmol, 87%) of preparation 20. 1H NMR (400 MHz, CDCl3) δ 7.32-7.27 (m, 2H), 7.03-7.07 (m, 2H), 6.91 (d, 1H, J=2.6 Hz), 6.72 (d, 1H, J=2.6 Hz), 5.17 (s, 2H), 5.11 (d, 1H, J=10.5 Hz), 5.09 (d, 1H, J=10.1 Hz), 5.03 (bs, 1H), 4.73 (dd, 1H, J=6.6, 13.2 Hz), 4.68 (dd, 1H, J=6.6, 13.2 Hz), 3.66 (dt, 1H, J=3.5, 8.8 Hz), 3.47 (s, 3H), 3.46 (s, 3H), 2.86 (ddt, 1H, J=2.2, 10.1, 7.5 Hz), 2.72 (m, 1H), 2.31 (m, 1H), 2.18 (t, 1H, J=6.6 Hz), 2.13 (m, 1H), 1.86 (dt, 1H, J=7.5, 14.5 Hz).
