反応 #57804

反応方程式

4-acetyl-N-[4-chloro-2-(hydroxy-pyridin-4-yl-methyl)-phenyl]-benzenesulfonamide

THF

BF3

AcOH

→

N-[4-chloro-2-(pyridine4-carbonyl)-phenyl]-4-(2-methyl[1,3]dioxolan-2-yl)-benzenesulfonamide

溶媒

ethylene glycol

Et2O

反応条件

後処理

1. 1
   その他was prepared in a vial
2. 2
   温度The vial was heated
3. 3
   温度cooled for one minute
4. 4
   workup.WAITleft standing
5. 5
   その他an LC-MS sample was taken after 1 minute of reaction
6. 6
   その他After another minute the reaction mixture was partitioned between 10 mL DCM and 10 mL H2O
7. 7
   workup.ADDITIONTo the reaction mixture was then added an additional 20 mL DCM and 20 mL aqueous 1 M NaOH
8. 8
   その他The DCM layer was collected
9. 9
   抽出the aqueous layer was extracted with DCM (2×20 mL)
10. 10
    濃縮concentrated by rotary evaporation
11. 11
    その他The product was isolated by preparative HPLC
12. 12
    workup.ADDITIONthe fractions containing the product
13. 13
    濃縮were concentrated to a volume of 15 mL
14. 14
    workup.ADDITIONTo this solution was added 3 mL 3 M NaOH and 0.52 g KMnO4
15. 15
    workup.STIRRINGThe reaction was stirred at RT
16. 16
    workup.ADDITIONwas added at intervals of ca. 2 hours
17. 17
    その他After a total rxn time of ca. 5 h
18. 18
    抽出extracted with DCM (125 mL)
19. 19
    洗浄washed with saturated aqueous NaHCO3
20. 20
    その他The DCM was removed by rotary evaporation
21. 21
    その他the product was obtained by preparative HPLC

実験手順

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).

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