反应详情

温度

2.5 °C

To a solution of 1-[4-(2-carboxy-ethoxy)-phenyl]-cyclopropanecarboxylic methyl ester (5.0 g, 20 mmol) in CH2Cl2 (50 mL) were added oxalyl chloride (4.8 g, 38 mmol) and two drops of DMF at 0° C. The mixture was stirred at 0-5° C. for 1 h and then evaporated under vacuum. To the resulting mixture was added CH2Cl2 (50 mL) at 0° C. and stirring was continued at 0-5° C. for 1 h. The reaction was slowly quenched with water and was extracted with EtOAc (50 mL×3). The combined organic extracts were dried over anhydrous Na2SO4 and evaporated under vacuum to give the crude product, which was purified by column chromatography on silica gel (petroleum ether/ethyl acetate 20:1-2:1) to give 1-(4-oxochroman-6-yl)cyclopropanecarboxylic acid (830 mg, 19%) and methyl 1-(4-oxochroman-6-yl)cyclopropanecarboxylate (1.8 g, 38%). 1-(4-Oxochroman-6-yl)cyclopropane-carboxylic acid: 1H NMR (400 MHz, DMSO) δ 12.33 (br s, 1 H), 7.62 (d, J=2.0 Hz, 1 H), 7.50 (dd, J=2.4, 8.4 Hz, 1 H), 6.95 (d, J=8.4 Hz, 1 H), 4.50 (t, J=6.4 Hz, 2 H), 2.75 (t, J=6.4 Hz, 2 H), 1.44-1.38 (m, 2 H), 1.10-1.07 (m, 2H). MS (ESI) m/z (M+H+) 231.4. 1-(4-Oxochroman-6-yl)cyclopropanecarboxylate: 1H NMR (400 MHz, CDCl3) δ 7.83 (d, J=2.4 Hz, 1 H), 7.48 (dd, J=2.4, 8.4 Hz, 1 H), 6.93 (d, J=8.4 Hz, 1 H), 4.55-4.52 (m, 2 H), 3.62 (s, 3 H), 2.80 (t, J=6.4 Hz, 2 H), 1.62-1.56 (m, 2 H), 1.18-1.15 (m, 2H).

1. customevaporated under vacuum
2. additionTo the resulting mixture was added CH2Cl2 (50 mL) at 0° C.
3. stirringstirring
4. waitwas continued at 0-5° C. for 1 h
5. customThe reaction was slowly quenched with water
6. extractionwas extracted with EtOAc (50 mL×3)
7. dry with materialThe combined organic extracts were dried over anhydrous Na2SO4
8. customevaporated under vacuum
9. customto give the crude product, which
10. customwas purified by column chromatography on silica gel (petroleum ether/ethyl acetate 20:1-2:1)