反应详情

2,3-Difluoro-5-iodobenzoic acid (Preparation 19, 18.2 g) in tetrahydrofuran (100 mL) at room temperature is treated with 1,1′-carbonyldiimidazole (12.46 g) portion-wise over a one minute period under a nitrogen atmosphere and the mixture is stirred for 6 h. In a separate flask, ethyltrimethylsilyl malonate (14.38 g) in tetrahydrofuran (40 mL) is cooled to 0-5° C. and DBU (11.20 g) is added dropwise over a period of 15 minutes. After 5.5 h, this solution is cannulated into the ice cooled imidazolide solution over a 7 minute period with vigorous stirring. The mixture is allowed to slowly warm to room temperature overnight. The reaction mixture is poured into 600 mL of ice/water containing 41 mL of 6N HCl. The mixture is extracted 3 times with ethyl acetate. The combined organic extracts are dried (Na2SO4) and concentrated in vacuo. The crude product is purified by chromatography, using 600 g of silica gel, packed and eluted with methylene chloride/heptane/ethyl acetate/acetic acid (3/7/0.5%/0.5%), to afford the title compound in 65% yield as an orange oily solid. Physical characteristics: 1H NMR (CDCl3) δ12.65, 8.00, 7.94, 7.73, 7.58, 5.81, 4.35-4.19, 3.96, 1.35, 1.28; IR (diffuse reflectance) 2986, 1647, 1622, 1573, 1489, 1420, 1383, 1293, 1275, 1240, 1215, 1037, 958, 882, 801 cm−1; MS (EI) m/z 354 (M+); HRMS (FAB) m/z 354.9648 (C11H9F2IO3+H). Anal. Found: C, 37.34; H, 2.50; N, 0.15.

1. waitAfter 5.5 h
2. extractionThe mixture is extracted 3 times with ethyl acetate
3. dry with materialThe combined organic extracts are dried (Na2SO4)
4. concentrationconcentrated in vacuo
5. customThe crude product is purified by chromatography
6. washeluted with methylene chloride/heptane/ethyl acetate/acetic acid (3/7/0.5%/0.5%)