反应详情

A 3 neck flask was equipped with a magnetic stirrer, 2 dropping funnels, a condenser and a nitrogen atmosphere. In the flask was placed 7.56g (116 mmol) of activated zinc (made by stirring zinc dust in 2% hydrochloric acid for 1/2 hour, filtering, washing with alcohol, acetone then ether and drying in vacuum) and 220 mL of anhydrous tetrahydrofuran (dried over sodium/benzophenone and distilled). In one dropping funnel was placed ethyl bromodifluoroacetate (23.62 g, 0.116 mol) and in the other was placed 13.90g (42mmole based on 65% purity) of N-(tert-butyloxycarbonyl) leucinal and anhydrous tetrahydrofuran (30 mL). The contents of the flask was heated to reflux and the ethyl bromodifluoroacetate was added at a rapid controlled rate. This was followed immediately by the addition of the aldehyde solution. The resulting mixture was refluxed an additional 15 minutes and then cooled for 10 minutes. Then a mixture of 75 mL saturated aqueous sodium chloride and 75 ml of IM potassium bisulfate was added. The resulting mixture was stirred for 15 minutes and was filtered through celite. The filter cake was washed with ethyl acetate. The combined filtrate was separated by phase. The aqueous layer was extracted with ethyl acetate (2×50 ml) and the combined organic phases were dried over MgSO4. Solvent was removed under vacuum to give 20.71 g of oil. This product was put on silica column and was eluted with 20% ethyl acetate in hexane for a crude separation. Product containing fractions were chromatographed on a Waters Prep 500 HPLC. The chromatography was done on silica and the eluent was 20% ethyl acetate in hexane. Two isomers were collected: 4.21 g of the 3(R), 4(S) isomer (mp 72°-76° C.) and 0.58 g of the 3(S), 4(S) isomer, and oil. In addition 0.43 g of a mixture of isomers from middle cuts was collected.

1. customA 3 neck flask was equipped with a magnetic stirrer
2. filtrationfiltering
3. washwashing with alcohol, acetone
4. dry with materialether and drying in vacuum) and 220 mL of anhydrous tetrahydrofuran (dried over sodium/benzophenone and distilled)
5. temperatureThe contents of the flask was heated
6. temperatureto reflux
7. temperatureThe resulting mixture was refluxed an additional 15 minutes
8. temperaturecooled for 10 minutes
9. additionwas added
10. filtrationwas filtered through celite
11. washThe filter cake was washed with ethyl acetate
12. customThe combined filtrate was separated by phase
13. extractionThe aqueous layer was extracted with ethyl acetate (2×50 ml)
14. dry with materialthe combined organic phases were dried over MgSO4
15. customSolvent was removed under vacuum