Potassium Sodium Tartrate → 2-(4-Chloro-phenyl)-4-(2-hydroxy-ethyl)-thiazole-5-carboxylic acid [3-methoxy-4-(4-triisopropylsilanyloxy-piperidin-1-yl)-phenyl]-amide

Participants

Reaction Steps

Dissolve the above 3-methoxy-4-(4-triisopropylsilanyloxy-piperidin-1-yl)-phenylamine (1.41 g, 3.72 mmol) in CH2Cl2 and add a trimethylaluminum solution (2.0M in hexanes, 2.25 mL, 4.50 mmol). Stir the solution at room temperature for 1 h, then add solid 2-(4-chloro-phenyl)-6,7-dihydro-pyrano[4,3-d]thiazol-4-one (1.01 g, 3.80 mmol) and continue stirring at room temperature overnight. Carefully quench reaction with saturated Rochelle's salt solution (15 mL) and stir at room temperature for 1 h. Extract the mixture with CH2Cl2 (3×20 mL). Combine all organic solutions, dry, filter, and concentrate in vacuo. Purify the crude material by flash chromatography using 2N NH3/MeOH in CH2Cl2 as eluent to give the title compound as a sold (1.00 g, 42%). MS (ES+) 644.0 (M+1)+, (ES−) 642.3 (M−1)−. 1H NMR (400 MHz, CDCl3): δ 10.76 (s, 1H), 8.00 (d, 2H, J=8.4 Hz), 7.60 (d, 2H, J=8.8 Hz), 7.35 (d, 1H, J=2.2 Hz), 7.13 (dd, 1H, J=8.8, 2.2 Hz), 6.88 (d, 1H, J=8.8 Hz), 5.78 (t, 1H, J=4.4 Hz), 3.94-3.86 (m, 3H), 3.78 (s, 3H), 3.21-3.13 (m, 4H), 2.78-2.70 (m, 2H), 1.93-1.85 (m, 2H), 1.67-1.57 (m, 2H), 1.06-1.04 (m, 21H).

Provenance & Evidence