反应详情

温度

-78 °C

To a solution of 1.441 g (14.2405 mmol) of diisopropylamine in 30 ml dry tetrahydrofuran under argon at -78° C. was added dropwise 9 ml of 1.6M (14.4 mmol) n-butyllithium in hexane. After stirring this solution at -78° C. for 1 hour, it was treated dropwise with a solution of 2.95 g (13.389 mmol) of 4,4-dimethyl-6-acetylthiochroman in 5 ml of dry tetrahydrofuran. After another hour of stirring at -78° C., the solution was treated with 2.507 g (14.53 mmol) of diethyl chlorophosphate and brought to room temperature, where it was stirred for 3.75 hours. This solution was then transferred using a double ended needle to a solution of lithium diisopropylamide (prepared as above using 2,882 g (28,481 mmol) of diisopropylamine and 18 ml of 1.6M (28.8 mmol) n-butyllithium in hexane) in 60 ml dry tetrahydrofuran at -78° C. The cooling bath was removed and the solution stirred at room temperature for 15 hours, then quenched with water and acidified to pH 1 with 3N hydrogen chloride. The mixture was stirred at room temperature for 12 hours, then treated with 65 ml water and 33 ml conc. hydrogen chloride and heated at reflux for 0.5 hours. After being cooled to room temperature, the organic layer was separated and the aqueous layer extracted with 5×50 ml benzene. The recovered organic fractions were combined and washed with 5% sodium carbonate solution, water, saturated NaCl solution and then dried (MgSO4). The solvent was removed in vacuo and the residue purified by flash chromatography (silica; 5% ethyl acetate in hexanes) followed by kugelrohr distillation (150° C., 0.7 mm) to give the captioned compound as a pale yellow oil.

1. stirringAfter another hour of stirring at -78° C.
2. custombrought to room temperature
3. stirringwhere it was stirred for 3.75 hours
4. customat -78° C
5. customThe cooling bath was removed
6. stirringthe solution stirred at room temperature for 15 hours
7. customquenched with water
8. stirringThe mixture was stirred at room temperature for 12 hours
9. additiontreated with 65 ml water and 33 ml conc. hydrogen chloride
10. temperatureheated
11. temperatureat reflux for 0.5 hours
12. temperatureAfter being cooled to room temperature
13. customthe organic layer was separated
14. extractionthe aqueous layer extracted with 5×50 ml benzene
15. washwashed with 5% sodium carbonate solution, water, saturated NaCl solution
16. dry with materialdried (MgSO4)
17. customThe solvent was removed in vacuo
18. customthe residue purified by flash chromatography (silica; 5% ethyl acetate in hexanes)
19. distillationfollowed by kugelrohr distillation (150° C., 0.7 mm)