Cesium carbonate → HCID 58746181, compound

HRID 724286Notes

Reaction equation

HRID 724286 reaction equation
[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[N:7][C:6]=1Cl)[CH3:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:20][S:21][C:22]1[CH:27]=[CH:26][C:25]([OH:28])=[CH:24][CH:23]=1>C1(C)C=CC=CC=1.CN1CCCC1.[Cu](I)I>[CH2:1]([O:3][C:4](=[O:13])[C:5]1[CH:10]=[C:9]([F:11])[CH:8]=[N:7][C:6]=1[O:28][C:25]1[CH:26]=[CH:27][C:22]([S:21][CH3:20])=[CH:23][CH:24]=1)[CH3:2]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 140864-(Methylthio)phenolHCID 11390082Ethyl 2-chloro-5-fluoronicotinate

Product 1

HCID 58746181HCID 58746181, compoundYield 69.2%

Reagents, catalysts & solvents 2

HCID 83717Copper iodideCatalystHCID 21877185HCID 21877185, compoundSolvent

Procedure

To a suspension of ethyl-2-chloro-5-fluoro-nicotinate (2.00 g, 9.82 mmol) and caesium carbonate (4.48 g, 13.8 mmol) in toluene/N-methylpyrrolidine (4:1, 50 ml) was added 4-methylsulfanylphenol (1.51 g, 10.8 mmol) at room temperature under nitrogen. Copper iodide (94 mg, 0.49 mmol) and the reaction was heated to 100° C. and stirred at this temperature for 17 h. The reaction was cooled to room temperature, partitioned between water (100 ml) and ethyl acetate (200 ml) and filtered. The filtrate was separated and the organic phase washed with brine (50 ml), dried over MgSO4 and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with toluene:ethyl acetate (95:5, by volume) and the product was triturated with pentane (10 ml) to give 5-fluoro-2-(4-methylsulfanyl-phenoxy)-nicotinic acid ethyl ester (2.09 g) as a yellow oil.

Workup

  1. custompartitioned between water (100 ml) and ethyl acetate (200 ml)
  2. filtrationfiltered
  3. customThe filtrate was separated
  4. washthe organic phase washed with brine (50 ml)
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by flash column chromatography on silica gel eluting with toluene:ethyl acetate (95:5, by volume)
  8. customthe product was triturated with pentane (10 ml)

Sources & evidence

ORD record
ord-81b6ac269f9940e2a3bd00190848ebf4
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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