Potassium Carbonate → 5-chloro-2-fluoro-N-(5-fluoropyridin-2-yl)-4-[2-piperidin-4-yl-4-(trifluoromethyl)phenoxy]benzenesulfonamide

HRID 46249Notes

Reaction equation

HRID 46249 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([F:11])([F:10])[F:9])=[CH:4][C:3]=1[CH:12]1[CH2:17][CH2:16][N:15](C(OC(C)(C)C)=O)[CH2:14][CH2:13]1.[Cl:25][C:26]1[C:27](F)=[CH:28][C:29]([F:46])=[C:30]([S:32]([N:35]([C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][N:40]=2)COC)(=[O:34])=[O:33])[CH:31]=1.C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.C(OCC)(=O)C.O>[Cl:25][C:26]1[C:27]([O:1][C:2]2[CH:7]=[CH:6][C:5]([C:8]([F:9])([F:10])[F:11])=[CH:4][C:3]=2[CH:12]2[CH2:13][CH2:14][NH:15][CH2:16][CH2:17]2)=[CH:28][C:29]([F:46])=[C:30]([S:32]([NH:35][C:39]2[CH:44]=[CH:43][C:42]([F:45])=[CH:41][N:40]=2)(=[O:34])=[O:33])[CH:31]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 594364985-chloro-2,4-difluoro-N-(5-fluoropyridin-2-yl)-N-(methoxymethyl)benzenesulfonamideHCID 59436542Tert-butyl4-[2-hydroxy-5-(trifluoromethyl)phenyl]piperidine-1-carboxylate

Product 1

HCID 468412145-chloro-2-fluoro-N-(5-fluoropyridin-2-yl)-4-[2-piperidin-4-yl-4-(trifluoromethyl)phenoxy]benzenesulfonamide

Reagents, catalysts & solvents 3

HCID 679Dimethyl SulfoxideSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
50 °C

Procedure

A mixture of tert-butyl 4-[2-hydroxy-5-(trifluoromethyl)phenyl]piperidine-1-carboxylate (Preparation 317, 51 mg, 0.15 mmol), 5-chloro-2,4-difluoro-N-(5-fluoropyridin-2-yl)-N-(methoxymethyl)benzenesulfonamide (Preparation 349, 50 mg, 0.1 mmol) and potassium carbonate (28 mg, 0.20 mmol) in anhydrous dimethyl sulfoxide (2 mL) was heated at 50° C. for 30 minutes. The reaction mixture was cooled to room temperature and diluted with ethyl acetate and water. The layers were separated and the aqueous layer extracted with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, water, dried over magnesium sulfate and concentrated in vacuo to afford the title compound as a light yellow thick oil, which was used in the next step without further purification. The residue was diluted with dichloromethane (2 mL), trifluoroacetic acid (210 uL, 2.7 mmol) was added and solution stirred at room temperature for 18 hours. The reaction solution was concentrated in vacuo and purified by preparative HPLC to afford the title compound as a white powder, 55.3 mg (as the trifluoroacetic acid salt)

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. customThe layers were separated
  3. extractionthe aqueous layer extracted with ethyl acetate
  4. washThe combined extracts were washed with saturated aqueous sodium chloride solution, water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-042e6bd49c0541e9a9ea261dcf56f1e0
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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