تفاعل #414194

ord-2be42446ab4248439eb14bf53a2ccb7e

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    workup.ADDITIONThe reaction temperature was kept between 20° C. and 27° C. during the addition
  2. 2
    أخرىThe phases were separated
  3. 3
    تجفيفthe organic phase dried with magnesium sulfate
  4. 4
    ترشيحfiltered
  5. 5
    تركيزconcentrated
  6. 6
    أخرىto yield 7.8 g of the crude product as a brown oil
  7. 7
    workup.STIRRINGAfter stirring for 10 minutes
  8. 8
    درجة الحرارةthe reaction temperature was slowly increased to 90° C. for 2.5 hours
  9. 9
    درجة الحرارةto cool to room temperature
  10. 10
    workup.WAITstand overnight
  11. 11
    استخلاصthe aqueous mixture was extracted with 200 ml of ethyl acetate
  12. 12
    أخرىthe phases separated
  13. 13
    غسيلthe organic phase washed with 100 ml of saturated sodium bicarbonate solution
  14. 14
    تجفيفdried with magnesium sulfate
  15. 15
    ترشيحfiltered
  16. 16
    تركيزconcentrated
  17. 17
    أخرىto yield the crude product as an oil
  18. 18
    أخرىflash chromatographed on Merck silica gel (230-400 mesh)
  19. 19
    تركيزconcentrated

الإجراء التجريبي

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.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US05272128uspto-grants-1993_12