反应详情

温度

55 °C

To a 250 ml 3N-RB flask fitted with a gas inlet, thermometer, overhead stirrer and a 125 ml pressure equalizing dropping funnel was added 26.5 g triethylamine. The triethylamine was cooled to 5° C. using a water/ice bath. Once the triethylamine was at 5° C. the methacrylic acid was added dropwise over a 20-25 min period. The mixture exothermed ˜10° C. After the addition was complete the water/ice bath was removed. While the solution was stirring (20 min) the dropping funnel was removed and replaced with a clean 125 ml pressure equalizing dropping funnel. The bromolactone (41.25 g)/THF (62.5 ml) was added dropwise over a 30 min. The mixture warmed from ˜18° C. to ˜30° C. with a precipitate forming. The reaction was heated to 55° C. and held at 55° C. for 16 hrs using an oil bath/hot plate. After heating for 16 hrs the mixture was cooled to 20° C. using a water/ice bath. The solid (44.5 g) was removed by vacuum filtration. The filtrates were reduced under partial pressure at 33-34° C. The resulting dark amber/brown oil was diluted with 90 g of methylene chloride. This solution was slowly poured onto a plug of silica gel (180 g, Baker 40 um flash chromatography packing) which had been pre-conditioned with methylene chloride. The crude mixture was allowed to pass into the silica gel plug by gravity. Once the crude mixture had passed the surface of the silica gel plug a fresh portion of methylene chloride was slowly poured onto the plug. The methylene chloride was pulled through the silica gel plug using reduced pressure. Once the methylene chloride had passed the surface of the silica gel plug the vacuum was removed then the next portion of methylene chloride was slowly poured onto the plug. This procedure was followed until all the product was extracted. The total filtrate was 850 ml. [The product was detected by spotting an aliquot on a TLC plate then illuminating with short UV.] To the orange filtrate was added 36 g of activated charcoal. The mixture was stirred for 1.5 hrs then filtered through a Celite plug (pre-conditioned with methylene chloride). The charcoal/Celite was washed with (2×100 ml, 1×50 ml methylene chloride). The filtrate was then washed with 2×200 ml D.I. water. The layers were separated and the organic layer was dried over 100 g of sodium sulfate. The mixture was stirred for 15-30 min. The sodium sulfate was removed and washed with 2×50 ml methylene chloride. The pale yellow filtrate (1.2 L) was stripped under reduced pressure at 33-34° C. leaving 36.4 g of a pale orange oil, Yield 85.6%.

1. customTo a 250 ml 3N-RB flask fitted with a gas inlet
2. customwas at 5° C.
3. additionwas added dropwise over a 20-25 min period
4. customexothermed ˜10° C
5. additionAfter the addition
6. customwas removed
7. customwas removed
8. additionThe bromolactone (41.25 g)/THF (62.5 ml) was added dropwise over a 30 min
9. temperatureThe mixture warmed from ˜18° C. to ˜30° C. with a precipitate
10. customforming
11. waitheld at 55° C. for 16 hrs
12. temperatureAfter heating for 16 hrs the mixture
13. temperaturewas cooled to 20° C.
14. customThe solid (44.5 g) was removed by vacuum filtration
15. customwere reduced under partial pressure at 33-34° C
16. additionThe resulting dark amber/brown oil was diluted with 90 g of methylene chloride
17. additionThis solution was slowly poured onto a plug of silica gel (180 g, Baker 40 um flash chromatography packing) which
18. additionwas slowly poured onto the plug
19. customwas removed
20. additionthe next portion of methylene chloride was slowly poured onto the plug
21. extractionwas extracted
22. customthen illuminating with short UV
23. addition] To the orange filtrate was added 36 g of activated charcoal
24. stirringThe mixture was stirred for 1.5 hrs
25. filtrationthen filtered through a Celite plug (pre-conditioned with methylene chloride)
26. washThe charcoal/Celite was washed with (2×100 ml, 1×50 ml methylene chloride)
27. washThe filtrate was then washed with 2×200 ml D.I
28. customThe layers were separated
29. dry with materialthe organic layer was dried over 100 g of sodium sulfate
30. stirringThe mixture was stirred for 15-30 min
31. customThe sodium sulfate was removed
32. washwashed with 2×50 ml methylene chloride
33. customwas stripped under reduced pressure at 33-34° C.