丁二酸单(2-三甲基硅乙基)醚

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-methyl-4-(4-(2-(1-(5-propylpyrimidin-2-yl)piperidin-4-yloxy)benzo[d]thiazol-6-yl)-5,6-dihydropyridin-1(2H)-ylsulfonyl)butan-2-ol (250 mg, 0.427 mmol), 4-oxo-4-(2-(trimethylsilyl)ethoxy)butanoic acid (compound 39B, 466 mg, 2.13 mmol), and 4-(pyrrolidin-1-yl)pyridine (95 mg, 0.640 mmol) in CH2Cl2 (8.6 mL) at rt was added DIC (332 μl 2.134 mmol). The mixture was heated to reflux for 5 h. The mixture was cooled to rt, diluted with CH2Cl2 (4 mL), and washed sequentially with cold aq. HCl (1 N, 3 mL), cold aq. NaHCO3 (10%, 2 mL), water (2 mL), and brine (2 mL). The organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 45% EtOAc) to afford Compound 39B as a light yellow solid (287 mg, 85% yield). 1H NMR (500 MHz, CDCl3) δ 8.14 (s, 2H), 7.65-7.54 (m, 2H), 7.36 (dd, J=8.4, 1.9 Hz, 1H), 6.10-5.97 (m, 1H), 5.42 (tt, J=7.8, 3.8 Hz, 1H), 4.26-4.09 (m, 4H), 4.01 (d, J=3.0 Hz, 2H), 3.70-3.61 (m, 2H), 3.56 (t, J=5.6 Hz, 2H), 3.11-3.01 (m, 2H), 2.69-2.61 (m, 2H), 2.56-2.45 (m, 4H), 2.42-2.33 (m, 2H), 2.28-2.18 (m, 2H), 2.15 (m, 2H), 1.91 (dtd, J=12.4, 8.2, 3.9 Hz, 2H), 1.55 (dd, J=15.0, 7.4 Hz, 2H), 1.45 (s, 6H), 0.92 (dd, J=13.0, 5.7 Hz, 4H), 0.02 (m, 2H), 0.00 (s, 9H). LCMS (m/z)=787 (M+H)+. The mixture was heated to reflux for 5 h washed sequentially with cold aq. HCl (1 N, 3 mL), cold aq. NaHCO3 (10%, 2 mL), water (2 mL), and brine (2 mL) The organic layer was dried (Na2SO4) filtered concentrated The residue was purified by column chromatography (silica gel, hexanes-EtOAc gradient 0 to 45% EtOAc)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Dihydrofuran-2,5-dione (8.0 g, 80 mmol) and 2-(trimethylsilyl)ethanol (5 g, 42.3 mmol) were dissolved in dry toluene (80 mL), followed by addition of DMAP (0.517 g, 4.23 mmol). The mixture was heated to reflux for 14 h. The mixture was cooled to rt, diluted with EtOAc (50 mL) and washed with aq. HCl (1 N, 3×30 mL). The organic layer was dried (Na2SO4), filtered, and concentrated to afford crude product as a white semi-solid (10.9 g, purity 85% as determined by 1H NMR, 100% yield), which is used in next reaction without further purification. The mixture was heated to reflux for 14 h washed with aq. HCl (1 N, 3×30 mL) The organic layer was dried (Na2SO4) filtered concentrated