反应详情

A solution of ethyl 2-(6-acetyl-4-chloro-3-fluoro-2-iodophenoxy)propanoate (3.58 g, 8.63 mmol) and 1,2-ethanediol (1.20 mL, 21.6 mmol) in toluene (16.3 mL) was treated with p-toluenesulfonic acid monohydrate (246 mg, 1.30 mmol) and heated at reflux in a flask fitted with a Dean-Stark trap filled with sieves. The reaction mixture was cooled and poured into saturated sodium bicarbonate (150 mL) and extracted with ethyl acetate (2×200 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered, and concentrated to give a crude residue. Purification by flash column chromatography (100% hexanes to 10% EtOAc/hexanes) gave the desired product (2.25 g, 57%) as a mixture of enantiomers. LCMS calculated for C15H18ClFIO5 (M+H)+: m/z=459.0; found: 459.0.

1. temperatureheated
2. temperatureat reflux in a flask
3. customfitted with a Dean-Stark trap
4. additionfilled with sieves
5. temperatureThe reaction mixture was cooled
6. extractionextracted with ethyl acetate (2×200 mL)
7. washThe combined organic layers were washed with brine
8. dry with materialdried over sodium sulfate
9. filtrationfiltered
10. concentrationconcentrated
11. customto give a crude residue
12. customPurification by flash column chromatography (100% hexanes to 10% EtOAc/hexanes)