反应详情

To the crude product from Example 1 in anhydrous THF (200 mL) is added N,N-diisopropylethylamine (25 mL, 143 mmol) followed by 2-bromomalonaldehyde (18.5 g, 123 mmol). The resulting mixture is allowed to stir at room temperature for 18 h, heated to 70° C. for 6 h, and then stirred at room temperature for an additional 18 h. The solvent is removed in vacuo and the residue is partitioned between EtOAc (400 mL) and water (350 mL). The water layer is back extracted with EtOAC (300 mL), the organic layers are combined, washed with brine (1×200 mL), dried over Na2SO4, filtered and the solvent removed in vacuo. The residue is purified by BIOTAGE® Silica gel chromatography on a 300 g Thompson Single Step silica cartridge using a linear gradient from 100% CH2Cl2 to 45% EtOAc/CH2Cl2 over 8 column volumes to give 3.5 g (17%, 2 steps) of the title compound as a tan solid. LC/MS (Condition A): ret. T=2.66 min, (M+Na) 265.09. 1H NMR (500 MHz, chloroform-d) δ ppm 9.73 (1 H, s), 7.86 (1 H, s), 4.05 (2 H, s), 1.49 (9 H, s).

1. temperatureheated to 70° C. for 6 h
2. stirringstirred at room temperature for an additional 18 h
3. customThe solvent is removed in vacuo
4. customthe residue is partitioned between EtOAc (400 mL) and water (350 mL)
5. extractionThe water layer is back extracted with EtOAC (300 mL)
6. washwashed with brine (1×200 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. customthe solvent removed in vacuo
10. customThe residue is purified by BIOTAGE® Silica gel chromatography on a 300 g Thompson Single Step silica cartridge