Potassium Carbonate → 4-{[3-Chloro-4-(trifluoromethyl)phenoxy]methyl}-N-[(dimethylamino)sulfonyl]-2,5-difluorobenzamide

HRID 1525643

Reaction equation

HRID 1525643 reaction equation
Br[CH2:2][C:3]1[C:17]([F:18])=[CH:16][C:6]([C:7]([NH:9][S:10]([N:13]([CH3:15])[CH3:14])(=[O:12])=[O:11])=[O:8])=[C:5]([F:19])[CH:4]=1.[Cl:20][C:21]1[CH:26]=[C:25]([OH:27])[CH:24]=[CH:23][C:22]=1[C:28]([F:31])([F:30])[F:29].C(=O)([O-])[O-].[K+].[K+]>CS(C)=O.ClCCl>[Cl:20][C:21]1[CH:26]=[C:25]([CH:24]=[CH:23][C:22]=1[C:28]([F:29])([F:30])[F:31])[O:27][CH2:2][C:3]1[C:17]([F:18])=[CH:16][C:6]([C:7]([NH:9][S:10]([N:13]([CH3:15])[CH3:14])(=[O:12])=[O:11])=[O:8])=[C:5]([F:19])[CH:4]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 136091473-Chloro-4-(trifluoromethyl)phenolHCID 896195864-(Bromomethyl)-N-[(dimethylamino)sulfonyl]-2,5-difluorobenzamide

Product 1

HCID 716160204-{[3-Chloro-4-(trifluoromethyl)phenoxy]methyl}-N-[(dimethylamino)sulfonyl]-2,5-difluorobenzamideYield 10.3%

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 4-(bromomethyl)-N-[(dimethylamino)sulfonyl]-2,5-difluorobenzamide (Preparation 1, 167 mg, 0.47 mmol) in dimethylsulfoxide (2 mL) was added 2-chloro-4-hydroxybenzotrifluoride (92 mg, 0.47 mmol) followed by addition of potassium carbonate (129 mg, 0.94 mmol). The reaction was left to stir at room temperature for 18 hours. The reaction was diluted with dichloromethane (20 mL) and washed with aqueous potassium hydrogen sulfate (5 mL). The organic phase was separated and the aqueous phase extracted with dichloromethane (2×20 mL). The combined organic layers were washed with brine (30 mL) and filtered through a phase separation cartridge. The solvent was removed under reduced pressure and the crude product purified by reverse phase preparative HPLC. The correct fractions were combined and reduced to dryness to afford the title compound as white solid (23 mg, 10%).

Workup

  1. waitThe reaction was left
  2. washwashed with aqueous potassium hydrogen sulfate (5 mL)
  3. customThe organic phase was separated
  4. extractionthe aqueous phase extracted with dichloromethane (2×20 mL)
  5. washThe combined organic layers were washed with brine (30 mL)
  6. filtrationfiltered through a phase separation cartridge
  7. customThe solvent was removed under reduced pressure
  8. customthe crude product purified by reverse phase preparative HPLC

Sources & evidence

ORD record
ord-2a9cf24699f942f9afe515c5343ee0f8
Source dataset
uspto-grants-2015_07
Patent number
US09085517B2

Linked notes

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