Potassium Carbonate → 4-methylphenyl 5-chloro-4-({5-chloro-6-[(1R)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluorobenzoate

HRID 2048098Notes

Reaction equation

HRID 2048098 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([OH:15])[CH:5]=[N:6][C:7]=1[O:8][C@H:9]([CH3:14])[C:10]([F:13])([F:12])[F:11].[Cl:16][C:17]1[C:18](F)=[CH:19][C:20]([F:33])=[C:21]([CH:32]=1)[C:22]([O:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=1)=[O:23].C([O-])([O-])=O.[K+].[K+]>CS(C)=O>[Cl:16][C:17]1[C:18]([O:15][C:4]2[CH:5]=[N:6][C:7]([O:8][C@H:9]([CH3:14])[C:10]([F:11])([F:12])[F:13])=[C:2]([Cl:1])[CH:3]=2)=[CH:19][C:20]([F:33])=[C:21]([CH:32]=1)[C:22]([O:24][C:25]1[CH:30]=[CH:29][C:28]([CH3:31])=[CH:27][CH:26]=1)=[O:23]

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 58042518HCID 58042518, compoundHCID 666671105-chloro-6-[(1R)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-ol

Product 1

HCID 580423794-methylphenyl 5-chloro-4-({5-chloro-6-[(1R)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-yl}oxy)-2-fluorobenzoateYield 99%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Procedure

To a mixture of 5-chloro-6-[(1R)-2,2,2-trifluoro-1-methylethoxy]pyridin-3-ol (Preparation 235, 360 mg, 0.86 mmol) and 4-methylphenyl 5-chloro-2,4-difluorobenzoate (Preparation 12, 242 mg, 0.86 mmol) in DMSO (2 mL) was added K2CO3 (237 mg, 1.7 mmol) at room temperature under N2 and the resulting mixture was stirred for 5 hours. The reaction was quenched with water and extracted with DCM (3×5 mL). The mixture was filtered through a phase separation cartridge. The combined organic phases were washed with brine (3 mL) and filtered through another phase separation cartridge. The filtrate was dried by N2 blowing to give a crude product. The crude product was purified by silica gel column chromatography eluting with 0-40% EtOAc in heptane to give the title compound (429 mg, 99%) as colourless gum.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with DCM (3×5 mL)
  3. filtrationThe mixture was filtered through a phase separation cartridge
  4. washThe combined organic phases were washed with brine (3 mL)
  5. filtrationfiltered through another phase separation cartridge
  6. dry with materialThe filtrate was dried by N2 blowing
  7. customto give a crude product
  8. customThe crude product was purified by silica gel column chromatography
  9. washeluting with 0-40% EtOAc in heptane

Sources & evidence

ORD record
ord-2ed3bdc49471457b9b5df85340a6beae
Source dataset
uspto-grants-2013_11
Patent number
US08592629B2

Reaction notes

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