Cesium carbonate → 3-Chloro-5-(2-chloro-3-fluoro-5-methoxyphenoxy)benzonitrile

HRID 1157419Notes

Reaction equation

HRID 1157419 reaction equation
[Cl:1][C:2]1[C:7]([F:8])=[CH:6][C:5]([O:9][CH3:10])=[CH:4][C:3]=1[OH:11].C([O-])([O-])=O.[Cs+].[Cs+].[Cl:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25](F)[CH:26]=1)[C:22]#[N:23]>CN1C(=O)CCC1.CCOC(C)=O>[Cl:18][C:19]1[CH:20]=[C:21]([CH:24]=[C:25]([O:11][C:3]2[CH:4]=[C:5]([O:9][CH3:10])[CH:6]=[C:7]([F:8])[C:2]=2[Cl:1])[CH:26]=1)[C:22]#[N:23]

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 27348413-Chloro-5-fluorobenzonitrileHCID 445509672-Chloro-3-fluoro-5-methoxyphenol

Product 1

HCID 445492473-Chloro-5-(2-chloro-3-fluoro-5-methoxyphenoxy)benzonitrileYield 88%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Under a nitrogen atmosphere, 2-chloro-3-fluoro-5-methoxyphenol (50-2) (6.7 g, 37.9 mmol) was diluted in NMP (40 mL, 0.95 M). To this solution Cs2CO3 (24.73 g, 76 mmol) was added and the reaction was allowed to stir at room temperature for 5 minutes. Then, 3-chloro-5-fluorobenzonitrile (11.81 g, 76 mmol) was added to the reaction and it was then heated to 120° C. After 2 hours the reaction was cooled to room temperature and then diluted with EtOAc (40 mL). It was partitioned with water (20 mL) and then extracted with EtOAc (3×30 mL). The organic extracts were then washed with water (3×20 mL) and brine (1×20 mL), dried over sodium sulfate and concentrated. Silica gel chromatography (1%-15% EtOAc/Hexanes) gave 3-chloro-5-(2-chloro-3-fluoro-5-methoxyphenoxy)-benzonitrile (50-4) (10.4 g, 88%).

Workup

  1. temperaturewas then heated to 120° C
  2. temperatureAfter 2 hours the reaction was cooled to room temperature
  3. customIt was partitioned with water (20 mL)
  4. extractionextracted with EtOAc (3×30 mL)
  5. washThe organic extracts were then washed with water (3×20 mL) and brine (1×20 mL)
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated

Sources & evidence

ORD record
ord-0f1e127f205e4fd5b28d325e995c8a78
Source dataset
uspto-grants-2010_10
Patent number
US07807684B2

Reaction notes

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