反应详情

Under inert gas, 1.51 g of C-(2-chlorophenyl)-N-(2,4-dimethoxybenzyl)methanesulfonamide were initially charged in 30 ml of THF, and then, at a temperature of −78° C., 6.09 ml of a 1.6 N methyllithium solution in diethyl ether were added dropwise and the mixture was stirred at constant temperature for 10 minutes. Subsequently, 1.83 ml of acetone were added. After stirring for 10 minutes, the reaction solution was admixed with 2 ml of trifluoroacetic acid and the solvent was removed under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was washed with saturated aqueous sodium hydrogencarbonate solution and water, dried over MgSO4 and concentrated by rotary evaporation. The residue was dissolved in 20 ml of dichloromethane, and 3 ml of trifluoroacetic acid were added. After stirring at room temperature for 2 hours, the reaction solution was concentrated by rotary evaporation and the residue was taken up in a mixture of water and dichloromethane. The solid which precipitates out was analyzed by LCMS and 1H NMR and subsequently discarded, since no product was present. Another solid precipitated out of the filtrate, which was identified by LCMS as product-containing (512 mg). Since further product was present in both phases of the filtrate, the aqueous phase was extracted with dichloromethane, the combined organic phases were concentrated by rotary evaporation and the residue was purified by means of normal phase chromatography using a Flashmaster with an n-heptane/ethyl acetate gradient. The product-containing fractions were combined and concentrated by rotary evaporation (707 mg). This gave the product with a molecular weight of 263.7 g/mol (C10H14ClNO3S); MS (ESI): m/e=283 (M+H2O+H+).

1. stirringAfter stirring for 10 minutes
2. customthe solvent was removed under reduced pressure
3. dissolutionThe residue was dissolved in ethyl acetate
4. washthe solution was washed with saturated aqueous sodium hydrogencarbonate solution and water
5. dry with materialdried over MgSO4
6. concentrationconcentrated by rotary evaporation
7. dissolutionThe residue was dissolved in 20 ml of dichloromethane
8. addition3 ml of trifluoroacetic acid were added
9. stirringAfter stirring at room temperature for 2 hours
10. concentrationthe reaction solution was concentrated by rotary evaporation
11. additionthe residue was taken up in a mixture of water and dichloromethane
12. customThe solid which precipitates out
13. customAnother solid precipitated out of the filtrate, which
14. additionas product-containing (512 mg)
15. extractionthe aqueous phase was extracted with dichloromethane
16. concentrationthe combined organic phases were concentrated by rotary evaporation
17. customthe residue was purified by means of normal phase chromatography
18. concentrationconcentrated by rotary evaporation (707 mg)
19. customThis gave the product with a molecular weight of 263.7 g/mol (C10H14ClNO3S)