HRID540976

反应详情

EQUATION

反应方程式

HRID 540976 的结构方程式

CONDITIONS

反应条件

温度
0 °C

PROCEDURE

实验过程

A flask equipped with an overhead stirred, thermometer and addition funnel was placed under a nitrogen atmosphere then charged with (E)-hex-2-enoic acid (89.8 g, 787 mmol), EDCI (158.3 g, 826 mmol), HOBt (112.0 g, 826 mmol) and IPAc (890 mL) then cooled to 0±5° C. The addition funnel was charged with NMM (99.1 mL, 1.6 mol) which was then added to the reaction mixture maintaining the temperature at 0±5° C. The mixture was stirred for 30 minutes then cyclopropylamine (60.0 mL, 866 mmol) was added and the reaction allowed to warm to 25±5° C. over 16 hours. The reaction mixture was washed by adding hydrochloric acid (500 mL, 1.0 N) and the mixture stirred vigorously for 30 minutes then allowed to sit for 30 minutes; the layers were separated and the washing procedure repeated. Sodium hydroxide (500 mL, 1.0 N) was added and then the mixture stirred vigorously for 30 minutes then allowed to sit for 30 minutes; the layers were separated and base wash procedure repeated. Water (500 mL) was added and then the mixture stirred vigorously for 30 minutes then allowed to sit for 30 minutes; the layers were separated and the wash procedure repeated. The combined organic phases were concentrated under reduced pressure to ⅓ original volume then IPAc (600 mL) was added; this was repeated two times when a white precipitate formed. The slimy was then concentrated under atmospheric pressure to ⅔ original volume then cooled to 50±5° C. N-heptane (890 mL) was slowly added while the reaction was cooled to −5±5° C. and held at this temperature for 4 hours. The solid was filtered, washed with cold n-heptane (2×250 mL) and dried to provide compound 37 as a fine white solid. 1H NMR (500 MHz, d6-DMSO) 7.89 (s, 1H), 6.58 (dt, J=15.2, 7.0 Hz, 1H), 5.80 (dt, J=15.2, 1.3 Hz, 1H), 2.70-2.65 (m, 1H), 2.12-2.06 (m, 2H), 1.44-1.37 (m, 2H), 0.88 (t, J=7.3 Hz, 3H), 0.64-0.60 (m, 2H), 0.42-0.38 (m, 2H).

WORKUP

后处理

  1. customA flask equipped with an overhead
  2. additionthermometer and addition funnel
  3. additionwas then added to the reaction mixture
  4. temperaturemaintaining the temperature at 0±5° C
  5. stirringThe mixture was stirred for 30 minutes
  6. temperatureto warm to 25±5° C. over 16 hours
  7. washThe reaction mixture was washed
  8. additionby adding hydrochloric acid (500 mL, 1.0 N)
  9. stirringthe mixture stirred vigorously for 30 minutes
  10. customthe layers were separated
  11. additionSodium hydroxide (500 mL, 1.0 N) was added
  12. stirringthe mixture stirred vigorously for 30 minutes
  13. waitto sit for 30 minutes
  14. customthe layers were separated
  15. washbase wash procedure
  16. additionWater (500 mL) was added
  17. stirringthe mixture stirred vigorously for 30 minutes
  18. waitto sit for 30 minutes
  19. customthe layers were separated
  20. concentrationThe combined organic phases were concentrated under reduced pressure
  21. additionIPAc (600 mL) was added
  22. customformed
  23. concentrationThe slimy was then concentrated under atmospheric pressure
  24. temperaturethen cooled to 50±5° C
  25. additionN-heptane (890 mL) was slowly added while the reaction
  26. temperaturewas cooled to −5±5° C.
  27. waitheld at this temperature for 4 hours
  28. filtrationThe solid was filtered
  29. washwashed with cold n-heptane (2×250 mL)
  30. customdried