反应详情

A solution consisting of 0.21 g of 4-acetyl-N-[4-chloro-2-(hydroxy-pyridin-4-yl-methyl)-phenyl]-benzenesulfonamide, 2 mL anhydrous THF, 50 μL AcOH and 400 μL ethylene glycol was prepared in a vial. The vial was heated by swaying gently in front of a heat gun, cooled for one minute and 400 μL 46.5% BF3:Et2O were immediately added. The vial was quickly shaken, left standing and an LC-MS sample was taken after 1 minute of reaction. After another minute the reaction mixture was partitioned between 10 mL DCM and 10 mL H2O. To the reaction mixture was then added an additional 20 mL DCM and 20 mL aqueous 1 M NaOH. The pH of the aqueous layer was brought to 3 using HCl and then quickly brought to pH 8-9 using saturated NaHCO3. The DCM layer was collected, the aqueous layer was extracted with DCM (2×20 mL) and all organic layers were combined and concentrated by rotary evaporation. The product was isolated by preparative HPLC, and the fractions containing the product were concentrated to a volume of 15 mL. To this solution was added 3 mL 3 M NaOH and 0.52 g KMnO4. The reaction was stirred at RT, monitored by LC-MS and additional KMnO4 (0.55 g×2) was added at intervals of ca. 2 hours. After a total rxn time of ca. 5 h, the crude mixture was brought to pH 4 using 10% AcOH, extracted with DCM (125 mL) and washed with saturated aqueous NaHCO3. The DCM was removed by rotary evaporation and the product was obtained by preparative HPLC. MS: m/z 459 (M++1).

1. customwas prepared in a vial
2. temperatureThe vial was heated
3. temperaturecooled for one minute
4. waitleft standing
5. customan LC-MS sample was taken after 1 minute of reaction
6. customAfter another minute the reaction mixture was partitioned between 10 mL DCM and 10 mL H2O
7. additionTo the reaction mixture was then added an additional 20 mL DCM and 20 mL aqueous 1 M NaOH
8. customThe DCM layer was collected
9. extractionthe aqueous layer was extracted with DCM (2×20 mL)
10. concentrationconcentrated by rotary evaporation
11. customThe product was isolated by preparative HPLC
12. additionthe fractions containing the product
13. concentrationwere concentrated to a volume of 15 mL
14. additionTo this solution was added 3 mL 3 M NaOH and 0.52 g KMnO4
15. stirringThe reaction was stirred at RT
16. additionwas added at intervals of ca. 2 hours
17. customAfter a total rxn time of ca. 5 h
18. extractionextracted with DCM (125 mL)
19. washwashed with saturated aqueous NaHCO3
20. customThe DCM was removed by rotary evaporation
21. customthe product was obtained by preparative HPLC