反应详情

Ethyl (5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate (472 mg, 2.015 mmol) was dissolved in ethanol (20 mL). Iodine (511 mg, 2.015 mmol) and silver sulfate (628 mg, 2.015 mmol) were added and the reaction was stirred vigorously at room temperature, protected from light, for 1 hour. The reaction was diluted with ethyl acetate (75 mL) and filtered to remove solids. The filtrate was washed with sodium bisulfite (2×50 mL), water (70 mL), and brine (70 mL). The organic layer was dried over sodium sulfate, filtered, and concentrated. The residue was purified by flash chromatography on silica gel with 0 to 50% ethyl acetate/hexanes. Further purification by SFC on a chiral AD column with 15% IPA/heptanes removed a minor regioisomer and separated the two enantiomers of ethyl (6-iodo-5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate. 1H NMR (CDCl3, 500 MHz) δ 7.55 (s, 1H), 6.72 (s, 1H), 4.17 (m, 2H), 3.85 (s, 3H), 3.53 (m, 1H), 2.95-2.65 (m, 3H), 2.60-2.42 (m, 2H), 1.78 (m, 1H), 1.28 (t, J=7.1 Hz, 3H).

1. customfor 1 hour
2. filtrationfiltered
3. customto remove solids
4. washThe filtrate was washed with sodium bisulfite (2×50 mL), water (70 mL), and brine (70 mL)
5. dry with materialThe organic layer was dried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated
8. customThe residue was purified by flash chromatography on silica gel with 0 to 50% ethyl acetate/hexanes
9. customFurther purification by SFC on a chiral AD column with 15% IPA/heptanes
10. customremoved a minor regioisomer
11. customseparated the two enantiomers of ethyl (6-iodo-5-methoxy-2,3-dihydro-1H-inden-1-yl)acetate