反应详情

To a 1-liter flask equipped with a condenser and a stirrer were added 470 mL of THF, 18.7 g of methyl iodide and 47 g of (4aR)-(10bR)-8-chloro-1,2,3,4,4a,5,6,10b-octahydrobenzo[f]quinolin-3-one, and stirring was begun at ambient temperature. To the mixture was added 100 ml of 50% aqueous sodium hydroxide in one portion, and gentle heating was begun. The temperature was raised as high as 41° and was then gradually lowered to 29° at the end of 16 hours of stirring. HPLC liquid chromatography, eluting with 1:1 acetonitrile:aqueous buffer (5% ammonium acetate) and monitoring at 220 nanometers, then showed that all the starting material had been consumed and the aqueous layer was removed. The organic layer was concentrated to an oil under vacuum, and the residue was dissolved in ethyl acetate. The solution was washed with brine, and the organic layer was washed with 200 mL of water twice, and was dried over magnesium sulfate and evaporated under vacuum while heptane was added portionwise as the ethyl acetate was removed. A total of 500 mL of heptane was added, and the product began to crystallize when about half of it had been added. The slurry was concentrated to about 300 ml, and filtered, and the solids were washed with heptane and dried in vacuum at 40°-50° to obtain 47.03 g of product, m.p. 97°-99°, of 98.7% purity.

1. customTo a 1-liter flask equipped with a condenser and a stirrer
2. customwas begun at ambient temperature
3. temperaturegentle heating
4. temperatureThe temperature was raised as high as 41°
5. customwas then gradually lowered to 29° at the end of 16 hours
6. stirringof stirring
7. washHPLC liquid chromatography, eluting with 1:1 acetonitrile
8. customhad been consumed
9. customthe aqueous layer was removed
10. concentrationThe organic layer was concentrated to an oil under vacuum
11. dissolutionthe residue was dissolved in ethyl acetate
12. washThe solution was washed with brine
13. washthe organic layer was washed with 200 mL of water twice
14. dry with materialwas dried over magnesium sulfate
15. customevaporated under vacuum while heptane
16. additionwas added portionwise as the ethyl acetate
17. customwas removed
18. additionA total of 500 mL of heptane was added
19. customto crystallize when about half of it
20. additionhad been added
21. concentrationThe slurry was concentrated to about 300 ml
22. filtrationfiltered
23. washthe solids were washed with heptane
24. customdried in vacuum at 40°-50°