反应详情

A solution of 5.65 g of O-isopropyl P-ethyl(hydroxymethyl)-phosphinate, (Example 22, Method B), 7.0 ml of triethylamine and 25 ml of methylene chloride was added dropwise over 45 minutes to a mixture of 50 ml of methylene chloride, 8.03 g of crude 2-methoxybenzenesulfonyl chloride, (Example 4), and 0.1 g of DMAP. The reaction temperature was kept between 20° C. and 27° C. during the addition. The reaction was allowed to stir at room temperature for four days and was then diluted with 80 ml of water and 100 ml of methylene chloride. The phases were separated, the organic phase dried with magnesium sulfate, filtered and concentrated to yield 7.8 g of the crude product as a brown oil. Phosphorus NMR indicated two products in a 1:1 ratio. The crude product was dissolved in 35 ml of acetic acid and 12 ml of 30% hydrogen peroxide solution was added. After stirring for 10 minutes, the reaction temperature was slowly increased to 90° C. for 2.5 hours. The reaction was allowed to cool to room temperature and stand overnight and was then poured onto 100 g of ice and the mixture diluted with 100 ml of water. After the ice had melted, the aqueous mixture was extracted with 200 ml of ethyl acetate, the phases separated, the organic phase washed with 100 ml of saturated sodium bicarbonate solution, dried with magnesium sulfate, filtered, and concentrated to yield the crude product as an oil. The oil was dissolved in 4 ml of methylene chloride and flash chromatographed on Merck silica gel (230-400 mesh) using blends of hexanes and ethyl acetate ranging from 30/70 to 10/90 hexanes and ethyl acetate, respectively. Similar fractions were combined and concentrated to yield 0.5 g of the desired product.

1. additionThe reaction temperature was kept between 20° C. and 27° C. during the addition
2. customThe phases were separated
3. dry with materialthe organic phase dried with magnesium sulfate
4. filtrationfiltered
5. concentrationconcentrated
6. customto yield 7.8 g of the crude product as a brown oil
7. stirringAfter stirring for 10 minutes
8. temperaturethe reaction temperature was slowly increased to 90° C. for 2.5 hours
9. temperatureto cool to room temperature
10. waitstand overnight
11. extractionthe aqueous mixture was extracted with 200 ml of ethyl acetate
12. customthe phases separated
13. washthe organic phase washed with 100 ml of saturated sodium bicarbonate solution
14. dry with materialdried with magnesium sulfate
15. filtrationfiltered
16. concentrationconcentrated
17. customto yield the crude product as an oil
18. customflash chromatographed on Merck silica gel (230-400 mesh)
19. concentrationconcentrated