反应详情

2-(6-Methoxymetoxy-2,5,7,8-tetramethylchroman-2-yl)ethyl p-toluenesulfonate (compound 4) (16.01 g, 35.7 mmol) was diluted in 200 mL of toluene, and piperazine (6.15 g, 71.4 mmol) was added to it, as shown in FIG. 5. The reaction solution was heated at reflux. TLC (silica gel 60 F254 plates; hexane:ethyl acetate (2:1) and chloroform:methanol (4:1)) indicated the reaction to be complete after 2.5 hours, and therefore, it was worked-up as follows: The reaction solution was cooled to room temperature (RT) which caused residual piperazine to precipitate out, and the piperazine was removed by filtration. The filter cake was rinsed with toluene, and this rinsing was combined with the filtrate. The filtrate was concentrated to an oil which weighed 15.79 g. The oil was diluted with chloroform (25 mL), and it was decanted onto a silica gel column (230-400 mesh, 60 Å) that had been prepared with chloroform:methanol (6:1) slurry. The flash column bed measured ˜5 cm×30 cm. The flash column was eluted with the following mobile phase systems: 1) CHCl3:MeOH (6:1); 3 L; -collected 40ט30 mL fractions, followed by 8ט100 mL fractions; 2) CHCl3:MeOH (2:1); 1.8 L; -collected 4×200 mL fractions, followed by 2×400 mL fractions; and 3) CHCl3:MeOH (1:1); 0.8 L; -collected 2×400 mL fractions. Based upon the TLC results of each fraction, appropriate fractions were combined and concentrated to a clear oil which weighed 10.70 g. The compound was characterized by NMR and MS as follows: 1) C-NMR (CDCl3): 12.25, 12.80, 13.68, 20.99, 24.42, 32.07, 36.59, 46.48, 54.42, 55.19, 57.88, 74.35, 99.89, 117.69, 123.28, 126,51, 128.45, 147.25, 148.16 ppm; 2) H-NMR (CDCl3): 1.23 (s, 3H), 1.78 (m, 5H), 2.05 (s, 3H), 2.12 (s, 3H), 2.16 (s, 3H), 2.39 (b, 4H), 2.48 (t, 2H), 2.57 (t, 2H), 286 (t, 4H), 3.59 (s, 3H), 4.82 (s, 2H) ppm; and 3) MS (ESI): 363.3 [M+H]+.

1. temperatureThe reaction solution was heated
2. temperatureat reflux
3. customthe reaction
4. customto precipitate out
5. customthe piperazine was removed by filtration
6. washThe filter cake was rinsed with toluene
7. concentrationThe filtrate was concentrated to an oil which
8. additionThe oil was diluted with chloroform (25 mL), and it
9. customwas decanted onto a silica gel column (230-400 mesh, 60 Å) that
10. customhad been prepared with chloroform:methanol (6:1) slurry
11. washThe flash column was eluted with the following mobile phase systems
12. customTLC results of each fraction, appropriate fractions
13. concentrationconcentrated to a clear oil which