HRID1376284

反应详情

EQUATION

反应方程式

HRID 1376284 的结构方程式

AUXILIARIES

试剂、催化剂与溶剂

3

CONDITIONS

反应条件

温度
0 °C

PROCEDURE

实验过程

The title compound was prepared as follows. (R)-5,5-Dimethyl-thiazolidine-3,4-dicarboxylic acid 3-tert-butyl ester 1 (1.0 g, 3.80 mmol) was dissolved in benzene (10 mL) and cooled to 0° C. with magnetic stirring. Two drops of DMF were added followed by a drop wise addition of oxalyl chloride (0.33 mL, 3.80 mmol). When gas evolution ceased, the solution was concentrated to a yellow/red residue. The material was dissolved in dry THF (10 mL) and cooled to −78° C. with magnetic stirring. The grignard reagent, 3-butenylmagnesium bromide (7.7 mL, 3.80 mmol) was added dropwise over 10 min. The result was stirred at −78° C. for 1 h then at −55° C. for 30 min. The reaction was quenched at −55° C. with sat NH4Cl soln.(3 mL) and then poured into H2O (50 mL). The mixture was extracted with EtOAc (2×50 mL). The combined organics were washed with brine (1×100 mL), dried over Na2SO4, filtered, and concentrated. The result was the amino ketone 26 that was sufficiently pure to use in the subsequent step. The clear oil 26 (0.24 g, 1.15 mmol) was dissolved in EtOAc (10 mL). AMB-AHPBA 4 (0.40 g, 1.09 mmol) was added followed by HOBt (0.15 g, 1.09 mmol). The mixture was stirred at room temperature lh, then cooled to 0° C. DCC (0.24 g, 1.15 mmol) was slowly added as solution in EtOAc (6 mL). The mixture was warmed to room temperature and stirred overnight. The mixture was filtered and the filtrate was washed with 1N HCl (10 mL), saturated NaHCO3 (10 mL), brine (10 mL), dried over Na2SO4 and concentrated to give a crude white solid (contaminated with DCU). The DCU was removed by flash chromatography (30% to 50% EtOAc in hexanes) to provide a white solid, which was dissolved in MeOH (2 mL) and treated with 4N HCl in 1,4-dioxane (0.26 mL, 1.1 mmol). The reaction was stirred at room temperature overnight then partitioned between 1N HCl (10 mL) and EtOAc (10 mL). The organic layer was washed with saturated sat. NaHCO3 (1×25 mL) dried over Na2SO4, filtered, and concentrated to a residue which was purified by flash chromatography (60% EtOAc in hexanes) to provide the title compound as a white amorphous solid: 1H NMR (DMSO-d6) δ 9.36 (s, 1H), 8.23 (d, J=8.1, 1H), 7.35–7.14 (m, 5H), 6.96 (t, J=7.5, 1H), 6.78 (d, J=8.2, 1H), 6.52 (d, J=7.5, 1H), 5.81–5.69 (m. 2H), 5.32 (d, J=9.7, 1H), 5.11–5.91 (m, 3H), 4.40 (m, 3H), 2.89–2.61 (m, 4H), 2.37–2.14 (m, 2H), 1.81 (s, 3H), 1.55 (s, 3H), 1.30 (s, 3H); Anal. Calcd for C28H34N2O5S: C, 65.86; H, 6.71; N, 5.49. Found: C, 65.52; H, 6.55; N, 5.81.

WORKUP

后处理

  1. customThe title compound was prepared
  2. concentrationthe solution was concentrated to a yellow/red residue
  3. dissolutionThe material was dissolved in dry THF (10 mL)
  4. temperaturecooled to −78° C. with magnetic stirring
  5. waitat −55° C. for 30 min
  6. customThe reaction was quenched at −55° C.
  7. addition(3 mL) and then poured into H2O (50 mL)
  8. extractionThe mixture was extracted with EtOAc (2×50 mL)
  9. washThe combined organics were washed with brine (1×100 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. concentrationconcentrated
  13. stirringThe mixture was stirred at room temperature lh
  14. temperaturecooled to 0° C
  15. temperatureThe mixture was warmed to room temperature
  16. stirringstirred overnight
  17. filtrationThe mixture was filtered
  18. washthe filtrate was washed with 1N HCl (10 mL), saturated NaHCO3 (10 mL), brine (10 mL)
  19. dry with materialdried over Na2SO4
  20. concentrationconcentrated
  21. customto give a crude white solid (contaminated with DCU)
  22. customThe DCU was removed by flash chromatography (30% to 50% EtOAc in hexanes)
  23. customto provide a white solid, which
  24. stirringThe reaction was stirred at room temperature overnight
  25. customthen partitioned between 1N HCl (10 mL) and EtOAc (10 mL)
  26. washThe organic layer was washed with saturated sat. NaHCO3 (1×25 mL)
  27. dry with materialdried over Na2SO4
  28. filtrationfiltered
  29. concentrationconcentrated to a residue which
  30. customwas purified by flash chromatography (60% EtOAc in hexanes)