反応 #2358578

反応方程式

methyl 4,6-dichloropicolinate

2-(4-(4-fluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Na2CO3

→

4,6-Dichloropicolinate

methyl 4-chloro-6-(4-(4-fluorophenoxy)phenyl)picolinate

溶媒

dioxane

反応条件

後処理

1. 1
   温度The vessel was heated
2. 2
   温度at reflux under nitrogen overnight
3. 3
   温度After cooling
4. 4
   その他the reaction was partitioned between 100 mL EtOAc and 50 mL brine
5. 5
   洗浄washed with additional brine
6. 6
   乾燥The organics were dried over MgSO4
7. 7
   ろ過filtered
8. 8
   濃縮concentrated in vacuo
9. 9
   workup.DISSOLUTIONThe residue was dissolved in MeOH (150 mL)
10. 10
    workup.ADDITIONconcentrated H2SO4 (1.5 mL) was added
11. 11
    温度The vessel was heated
12. 12
    温度at reflux under nitrogen overnight
13. 13
    温度After cooling the reaction
14. 14
    その他was quenched by addition of 10 g NaHCO3
15. 15
    その他The mixture was evaporated in vacuo
16. 16
    その他the residue partitioned between 100 mL EtOAc and 50 mL brine
17. 17
    洗浄The organics were washed once with 50 mL brine
18. 18
    抽出The combined aqueous washes were extracted once with 50 mL EtOAc
19. 19
    乾燥The combined organics were dried over MgSO4
20. 20
    ろ過filtered
21. 21
    濃縮concentrated in vacuo
22. 22
    その他The residue was chromatographed over silica gel eluting with 5-25% EtOAc in hexanes
23. 23
    その他The product fractions were isolated
24. 24
    その他evaporated in vacuo

実験手順

4,6-Dichloropicolinate was synthesized according to the procedures described in WO 2006/053227. To a solution of the methyl 4,6-dichloropicolinate (2.52 g, 12.2 mmol) in dioxane (100 mL) was added 2-(4-(4-fluorophenoxy)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.83 g, 12.2 mmol), 2M aqueous Na2CO3 solution (12.5 mL, 25 mmol) and PdCl2(dppf) (0.502 g, 0.62 mmol). The vessel was heated at reflux under nitrogen overnight. After cooling, the reaction was partitioned between 100 mL EtOAc and 50 mL brine and washed with additional brine. The organics were dried over MgSO4, filtered and concentrated in vacuo. The residue was dissolved in MeOH (150 mL) and concentrated H2SO4 (1.5 mL) was added. The vessel was heated at reflux under nitrogen overnight. After cooling the reaction was quenched by addition of 10 g NaHCO3. The mixture was evaporated in vacuo and the residue partitioned between 100 mL EtOAc and 50 mL brine. The organics were washed once with 50 mL brine. The combined aqueous washes were extracted once with 50 mL EtOAc. The combined organics were dried over MgSO4, filtered and concentrated in vacuo. The residue was chromatographed over silica gel eluting with 5-25% EtOAc in hexanes. The product fractions were isolated and evaporated in vacuo to yield the product methyl 4-chloro-6-(4-(4-fluorophenoxy)phenyl)picolinate as a pale tan oil (1.426 g, 3.99 mmol, 33% yield, LC/MS: m/z=358.1 [M+H]+).

出典