Water → 5-(4-Methoxy-3-methylphenyl)-3-(trifluoromethyl)-1,2,4-thiadiazole

HRID 603440Notes

Reaction equation

HRID 603440 reaction equation
Cl[C:2]1[S:6][N:5]=[C:4]([C:7]([F:10])([F:9])[F:8])[N:3]=1.[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][C:14]=1[CH3:22].O>COCCOC.C([O-])([O-])=O.[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:11][O:12][C:13]1[CH:18]=[CH:17][C:16]([C:2]2[S:6][N:5]=[C:4]([C:7]([F:10])([F:9])[F:8])[N:3]=2)=[CH:15][C:14]=1[CH3:22]

Participants

7

Reactant 3

HCID 962Water2×HCID 2773487(4-Methoxy-3-methylphenyl)boronic acidHCID 132795895-Chloro-3-(trifluoromethyl)-1,2,4-thiadiazole2×

Product 1

HCID 593005345-(4-Methoxy-3-methylphenyl)-3-(trifluoromethyl)-1,2,4-thiadiazole

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalyst2×HCID 80711,2-DimethoxyethaneSolvent2×HCID 10340Sodium CarbonateSolvent2×

Conditions

Temperature
80 °C

Procedure

5-Chloro-3-(trifluoromethyl)-1,2,4-thiadiazole (2.26 g, 12.0 mmol) (synthesis described in DE 3228147) was dissolved in 1,2-dimethoxyethane (50 mL) and 4-methoxy-3-methylphenylboronic acid (2.4 g, 14.4 mmol) and tetrakis(triphenylphosphine)palladium (0.1 g, 0.09 mmol) were added. After 1.5 h at rt, Na2CO3 (19.2 mL, 2M aqueous solution) was added and the mixture was stirred for 4 h at 80° C. and for 14 h at rt. Water was added and the mixture was extracted with ethyl acetate. The organic phase was dried over MgSO4, filtered, and concentrated under reduced pressure. Due to low conversion the crude product was again reacted with 5-chloro-3-(trifluoromethyl)-1,2,4-thiadiazole (2.4 g, 14.4 mmol), tetrakis(triphenylphosphine)palladium (0.1 g, 0.09 mmol) in DME (50 mL) and Na2CO3 (19.2 mL, 2M aqueous solution). After stirring at 80° C. for 16 h, the reaction mixture was cooled and water was added. The mixture was extracted with ethyl acetate, the organic phase dried over MgSO4, filtered and concentrated under reduced pressure. The crude product (3.2 g) had a purity of ˜90% and was used in the next step without further purification.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. dry with materialThe organic phase was dried over MgSO4
  3. filtrationfiltered
  4. concentrationconcentrated under reduced pressure
  5. stirringAfter stirring at 80° C. for 16 h
  6. temperaturethe reaction mixture was cooled
  7. extractionThe mixture was extracted with ethyl acetate
  8. dry with materialthe organic phase dried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customwas used in the next step without further purification

Sources & evidence

ORD record
ord-502e86395608455faa09d5e2b26c20ba
Source dataset
uspto-grants-2011_03
Patent number
US07906653B2

Reaction notes

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