Cesium carbonate → HCID 178503205, compound

HRID 724275Notes

Reaction equation

HRID 724275 reaction equation
[CH2:1]([O:8][C:9]([C@H:11]1[CH2:16][CH2:15][C@@H:14]([NH:17][C:18]([C:20]2[C:21](Cl)=[N:22][CH:23]=[C:24]([F:26])[CH:25]=2)=[O:19])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:28][S:29][C:30]1[CH:31]=[C:32]([OH:36])[CH:33]=[CH:34][CH:35]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C)C=O>[CH2:1]([O:8][C:9]([C@H:11]1[CH2:16][CH2:15][C@@H:14]([NH:17][C:18]([C:20]2[C:21]([O:36][C:32]3[CH:33]=[CH:34][CH:35]=[C:30]([S:29][CH3:28])[CH:31]=3)=[N:22][CH:23]=[C:24]([F:26])[CH:25]=2)=[O:19])[CH2:13][CH2:12]1)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 99204073-(Methylsulfanyl)phenolHCID 178523782HCID 178523782, compound

Product 1

HCID 178503205HCID 178503205, compoundYield 73.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

cis-4-[(2-Chloro-5-fluoro-pyridine-3-carbonyl)-amino]-cyclohexanecarboxylic acid benzyl ester (2.14 g, 5.5 mmol), 3-methylsulfanylphenol (844 mg, 6.02 mmol) and caesium carbonate (2.67 g, 8.21 mmol) were suspended in dimethylformamide (50 ml) and the reaction was heated to 65° C. and stirred at this temperature under nitrogen for 18 h. The reaction was cooled to room temperature, concentrated under reduced pressure and the residue was diluted with water (50 ml). It was then extracted with ethyl acetate (3×40 ml) and the combined organic extracts were washed with water (2×10 ml), brine (10 ml), dried over MgSO4 and the solvent removed under reduced pressure. The residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of pentane:ethyl acetate (2:8 changing to 1:3 then 3:7, by volume) to give cis-4-{[5-Fluoro-2-(3-methylsulfanyl-phenoxy)-pyridine-3-carbonyl]-amino}-cyclohexanecarboxylic acid benzyl ester (2.0 g) as a pale yellow oil.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. concentrationconcentrated under reduced pressure
  3. additionthe residue was diluted with water (50 ml)
  4. extractionIt was then extracted with ethyl acetate (3×40 ml)
  5. washthe combined organic extracts were washed with water (2×10 ml), brine (10 ml)
  6. dry with materialdried over MgSO4
  7. customthe solvent removed under reduced pressure
  8. customThe residue was purified by flash column chromatography on silica gel eluting with a solvent gradient of pentane:ethyl acetate (2:8 changing to 1:3

Sources & evidence

ORD record
ord-26c1273c36dc4236a1d38c17fd73ec01
Source dataset
uspto-grants-2006_11
Patent number
US07141586B2

Reaction notes

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