Acetic Acid → 3-Chloro-5-((1,2-dihydro-2-oxo-4-(trifluoromethyl)-3-pyridinyl)oxy)benzonitrile

HRID 1952333Notes

Reaction equation

HRID 1952333 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:17]=[C:18]([Cl:20])[CH:19]=1)[O:5][C:6]1[C:7](=[O:16])[NH:8][CH:9]=[CH:10][C:11]=1[C:12]([F:15])([F:14])[F:13].[Cu][C:22]#[N:23].CN1CCCC1=O.C(O)(=O)C>C(OCC)(=O)C>[Cl:20][C:18]1[CH:19]=[C:2]([CH:3]=[C:4]([O:5][C:6]2[C:7](=[O:16])[NH:8][CH:9]=[CH:10][C:11]=2[C:12]([F:15])([F:14])[F:13])[CH:17]=1)[C:22]#[N:23]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 13387N-methyl-2-pyrrolidoneHCID 58460053HCID 58460053, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 584600483-Chloro-5-((1,2-dihydro-2-oxo-4-(trifluoromethyl)-3-pyridinyl)oxy)benzonitrile

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

To a round bottom flask charged with 3-(3-bromo-5-chlorophenoxy)-4-(trifluoromethyl)pyridin-2(1H)-one (3.00 g, 8.14 mmol) and copper (I) cyanide (7.29 g, 81.0 mmol) was added N-methylpyrrolidinone (25 mL). This suspension under N2 was placed in an oil bath at 175° C. After 5 hours the reaction mixture was allowed to cool to room temperature. Glacial acetic acid (30 mL) was added to the mixture and stirred for 10 minutes. The mixture was diluted with ethyl acetate (100 mL), filtered through diatomaceous earth and the pad was washed with ethyl acetate (100 mL). The filtrate was washed with water (3×100 mL) and brine (2×100 mL). The organic fraction was dried (Na2SO4), filtered and the solvent was removed under reduced pressure to yield a solid. This was adsorbed onto silica gel and purified by column chromatography on a pre-packed silica gel Redi Sep 120 gram column, eluting with 0-5% methanol in CH2Cl2 to yield the title compound. 1H NMR (DMSO-d6) δ 12.70 (s, 1H), 7.76-7.72 (m, 1H), 7.62-7.56 (m, 2H), 7.54-7.52 (m, 1H), 6.48 (d, J=6.8 Hz, 1H). LRMS (M+1)=314.87.

Workup

  1. customThis suspension under N2 was placed in an oil bath at 175° C
  2. filtrationfiltered through diatomaceous earth
  3. washthe pad was washed with ethyl acetate (100 mL)
  4. washThe filtrate was washed with water (3×100 mL) and brine (2×100 mL)
  5. dry with materialThe organic fraction was dried (Na2SO4)
  6. filtrationfiltered
  7. customthe solvent was removed under reduced pressure
  8. customto yield a solid
  9. custompurified by column chromatography on a pre-packed silica gel Redi Sep 120 gram column
  10. washeluting with 0-5% methanol in CH2Cl2

Sources & evidence

ORD record
ord-2d0bd43a86954f35947c64f64e5cb36d
Source dataset
uspto-grants-2013_03
Patent number
US08404856B2

Reaction notes

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