Sodium Carbonate → HCID 20316405, compound

HRID 2271396Notes

Reaction equation

HRID 2271396 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:3]=1.[F:13][C:14]1[CH:35]=[CH:34][C:17]([O:18][C:19]2[CH:24]=[CH:23][C:22](B3OC(C)(C)C(C)(C)O3)=[CH:21][CH:20]=2)=[CH:16][CH:15]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:1][C:2]1[CH:7]=[C:6]([Cl:8])[N:5]=[C:4]([C:9]([O-:11])=[O:10])[CH:3]=1.[Cl:1][C:2]1[CH:7]=[C:6]([C:22]2[CH:21]=[CH:20][C:19]([O:18][C:17]3[CH:16]=[CH:15][C:14]([F:13])=[CH:35][CH:34]=3)=[CH:24][CH:23]=2)[N:5]=[C:4]([C:9]([O:11][CH3:12])=[O:10])[CH:3]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 18922464Methyl 4,6-dichloropyridine-2-carboxylateHCID 666684382-[4-(4-Fluorophenoxy)phenyl]-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 2

HCID 20316405HCID 20316405, compoundHCID 66666699HCID 66666699, compound

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Procedure

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]+).

Workup

  1. temperatureThe vessel was heated
  2. temperatureat reflux under nitrogen overnight
  3. temperatureAfter cooling
  4. customthe reaction was partitioned between 100 mL EtOAc and 50 mL brine
  5. washwashed with additional brine
  6. dry with materialThe organics were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue was dissolved in MeOH (150 mL)
  10. additionconcentrated H2SO4 (1.5 mL) was added
  11. temperatureThe vessel was heated
  12. temperatureat reflux under nitrogen overnight
  13. temperatureAfter cooling the reaction
  14. customwas quenched by addition of 10 g NaHCO3
  15. customThe mixture was evaporated in vacuo
  16. customthe residue partitioned between 100 mL EtOAc and 50 mL brine
  17. washThe organics were washed once with 50 mL brine
  18. extractionThe combined aqueous washes were extracted once with 50 mL EtOAc
  19. dry with materialThe combined organics were dried over MgSO4
  20. filtrationfiltered
  21. concentrationconcentrated in vacuo
  22. customThe residue was chromatographed over silica gel eluting with 5-25% EtOAc in hexanes
  23. customThe product fractions were isolated
  24. customevaporated in vacuo

Sources & evidence

ORD record
ord-c5497ce7a6f94f0eb1de30297e42dee3
Source dataset
uspto-grants-2015_09
Patent number
US09120752B2

Reaction notes

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