反应详情

温度

0 °C

To a solution of meso-2,3-bis-(4-chlorophenyl)-2,3-butanediamine (3 g, example 1) in toluene cooled to 0° C. was added dropwise 2 M solution of trimethylaluminum in toluene (5.33 mL, 10.66 mmol). After the addition, the mixture was stirred at 0° C. for 15 min then the ice bath was removed. After 30 min, the mixture was warmed up to 80-100° C. for about 30 min before being slowly cooled down to room temperature. At room temperature, a solution of 4-bromo-2-ethoxy-benzoic acid ethyl ester (3.18 g, 11.64 mmol) in toluene (10 mL) was added, and the yellow reaction mixture was heated at reflux for 48 h. Upon cooling to room temperature, 1 M Rochelle solution (˜20 mL) and ethyl acetate (˜50 mL) were added. The biphasic mixture was stirred rigorously at room temperature for 3 h. The layers were separated and the aqueous layer was extracted with ethyl acetate (1×100 mL). The combined organic layers were washed with saturated solution of sodium bicarbonate (1×20 mL), brine (1×20 mL), dried over anhydrous sodium sulfate. The solids were filtered off and the filtrate was concentrated to dryness. Purification of the crude residue by flash chromatography (120 g of silica gel, eluting with 5-10%, 20%, 40% then 80% ethyl acetate in hexane) gave the title compound as light yellow foam (3.25 g, 65%). HR-MS (ES, m/z) calculated for C25H24N2OCl2Br [(M+H)+] 517.0444, observed 517.0443.

1. additionAfter the addition
2. customthe ice bath was removed
3. waitAfter 30 min
4. temperaturethe mixture was warmed up to 80-100° C. for about 30 min
5. temperaturebefore being slowly cooled down to room temperature
6. temperaturethe yellow reaction mixture was heated
7. temperatureat reflux for 48 h
8. temperatureUpon cooling to room temperature
9. stirringThe biphasic mixture was stirred rigorously at room temperature for 3 h
10. customThe layers were separated
11. extractionthe aqueous layer was extracted with ethyl acetate (1×100 mL)
12. washThe combined organic layers were washed with saturated solution of sodium bicarbonate (1×20 mL), brine (1×20 mL)
13. dry with materialdried over anhydrous sodium sulfate
14. filtrationThe solids were filtered off
15. concentrationthe filtrate was concentrated to dryness
16. customPurification of the crude residue by flash chromatography (120 g of silica gel
17. washeluting with 5-10%, 20%, 40%