反应详情

温度

0 °C

Scheme IB, step B: A 500 mL three necked round bottom flask equipped with a mechanical stirrer, thermometer, reflux condenser, addition funnel and a nitrogen blanket is charged with triphenylphosphine (16.19 g, 61.73 mmol) and THF (200 mL). To the solution at 0° C. was added dropwise, a solution of diisopropyl azodicarboxylate (12.15 mL, 61.73 mmol) dissolved in THF (30 mL) over a period of 10 minutes. A massive precipitate formed immediately after addition. To the slurry was then added solid phthalimide (9.08 g, 61.73 mmol), followed by a solution of 5-phenylcyclopentane-1-ol (10.0 g, 61.73 mmol) dissolved in THF (30 mL) over a period of 20 minutes maintaining temperature at 0° C. to 5° C. (reaction mixture went into solution by the end of alcoholic substrate addition). Reaction was then stirred at 0° C. for 4.0 hours and brought to room temperature overnight for convenience. Quenched reaction with water (200 mL) and extracted organics with chloroform (200 mL). Washed the organic with water (100 mL) and dried with anhydrous magnesium sulfate. Subsequent filtration and concentration under reduced pressure afforded an oil which solidified on equilibrating to room temperature. To the precipitate was then added hexane (250.0 mL) with vigorous stirring. Filtered off triphenylphosphine oxide precipitate and concentrated filtrate to an oil. Silica gel plug filtration of the oil with 1:1 ethyl acetate:hexanes and subsequent concentration of product fractions afforded an off white precipitate of (+,−) Cis-2-(2-phenyl-cyclopentyl)-isoindole-1,3-dione (mass=12.5 g, 69.6%); 1H nmr (CDCl3) 6 1.6-1.8 (m, 1H), 2.0-2.1 (m, 1H), 2.2-2.35 (m, 2H), 2.4-2.68 (m, 2H), 3.39-3.5 (m, 1H), 5.0-5.1 (m, 1H), 6.9-7.15 (aromatic, 5H), 7.52-7.64 (aromatic, 4H); 13C (CDCl3) 6 25.4, 28.89, 30.56, 50.34, 54.60, 122.89, 126.44, 128.01, 128.41, 131.67, 139.68, 168.86).

1. temperaturethermometer, reflux
2. additioncondenser, addition funnel
3. additionTo the solution at 0° C. was added dropwise
4. customA massive precipitate formed immediately
5. additionafter addition
6. temperaturemaintaining temperature at 0° C. to 5° C. (
7. customreaction mixture
8. additionwent into solution by the end of alcoholic substrate addition)
9. customReaction
10. waitbrought to room temperature overnight for convenience
11. customQuenched
12. customreaction with water (200 mL)
13. extractionextracted organics with chloroform (200 mL)
14. washWashed the organic with water (100 mL)
15. dry with materialdried with anhydrous magnesium sulfate
16. filtrationSubsequent filtration and concentration under reduced pressure
17. customafforded an oil which
18. customsolidified on equilibrating to room temperature
19. filtrationFiltered off triphenylphosphine oxide precipitate and concentrated filtrate to an oil
20. filtrationSilica gel plug filtration of the oil with 1:1 ethyl acetate
21. concentrationhexanes and subsequent concentration of product fractions