Ethanol → Methyl 4-chloro-6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]-oxy}phenyl)methyl]-2-Pyridinecarboxylate

HRID 2356623Notes

Reaction equation

HRID 2356623 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8]Cl)[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=1.C(O)C.[Cl:17][C:18]1[CH:19]=[CH:20][C:21]([O:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=2[F:36])=[C:22](B(O)O)[CH:23]=1.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([CH2:8][C:20]2[CH:19]=[C:18]([Cl:17])[CH:23]=[CH:22][C:21]=2[O:27][CH2:28][C:29]2[CH:34]=[CH:33][C:32]([Cl:35])=[CH:31][C:30]=2[F:36])[N:5]=[C:4]([C:10]([O:12][CH3:13])=[O:11])[CH:3]=1

Participants

7

Reactant 4

HCID 702EthanolHCID 11430Potassium CarbonateHCID 59384250(5-Chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)boronic acidHCID 68456565Methyl 4-chloro-6-(chloromethyl)pyridine-2-carboxylate

Product 1

HCID 68458580Methyl 4-chloro-6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]-oxy}phenyl)methyl]-2-PyridinecarboxylateYield 12.8%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 1140TolueneSolvent

Procedure

To a stirring solution of methyl 4-chloro-6-(chloromethyl)-2-pyridinecarboxylate (175 mg), in dry toluene (4 ml) and ethanol (4 ml) was added (5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)boronic acid (250 mg), potassium carbonate (330 mg) and tetrakis(triphenylphosphine)-palladium(0) (92 mg). The mixture was stirred under reflux for 2 hours. Solvent was removed u.r.p. (under reduced pressure) and water (20 ml) and ether (20 ml) added to the residue. Insoluble solid was filtered off over Hyflo and washed with ether. The aqueous layer was separated off and washed with ether (15 ml), and the combined ether layers washed with brine (10 ml), dried over MgSO4 and evaporated down u.r.p. The residue was purified by mass-directed autopreparation to give a white solid (46.3 mg, 12.8%). LC/MS [MH+]=468/470/472, Rt=4.11 min. NMR and LC/MS indicated that trans-esterification had occurred to give the ethyl ester.

Workup

  1. temperatureunder reflux for 2 hours
  2. customSolvent was removed u.r.p
  3. addition(under reduced pressure) and water (20 ml) and ether (20 ml) added to the residue
  4. filtrationInsoluble solid was filtered off over Hyflo
  5. washwashed with ether
  6. customThe aqueous layer was separated off
  7. washwashed with ether (15 ml)
  8. washthe combined ether layers washed with brine (10 ml)
  9. dry with materialdried over MgSO4
  10. customevaporated down u.r.p
  11. customThe residue was purified by mass-directed autopreparation

Sources & evidence

ORD record
ord-206a81332f8d48e19ef464c15d786400
Source dataset
uspto-grants-2010_07
Patent number
US07759369B2

Reaction notes

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