Hydrochloric Acid → HCID 58385818, compound

HRID 1038348Notes

Reaction equation

HRID 1038348 reaction equation
C[C:2]([O-:5])(C)C.[K+].[CH2:7]([C:9]1[CH:14]=[CH:13][C:12]([CH2:15][C:16](OCC)=O)=[CH:11][CH:10]=1)[CH3:8].[Br:21][C:22]1[CH:27]=C(F)[C:25]([C:29]#[N:30])=[C:24](F)[CH:23]=1.[OH-].[Na+].Cl>CN1C(=O)CCC1.CO>[Br:21][C:22]1[CH:27]=[C:16]([CH2:15][C:12]2[CH:11]=[CH:10][C:9]([CH2:7][CH3:8])=[CH:14][CH:13]=2)[C:25]([C:29]#[N:30])=[C:24]([O:5][CH3:2])[CH:23]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 14798Sodium HydroxideHCID 27569164-Bromo-2,6-difluorobenzonitrileHCID 23665647Potassium tert-butoxideHCID 53419404Ethyl 2-(4-ethylphenyl)acetate

Product 1

HCID 58385818HCID 58385818, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 13387N-methyl-2-pyrrolidoneSolvent2×

Procedure

KOtBu (11.8 g) is added to a flask charged with a stir bar and dry NMP (40 mL) and chilled to −10° C. under argon atmosphere. A solution of ethyl (4-ethyl-phenyl)-acetate (10.1 g) and 1-bromo-4-cyano-3,5-difluoro-benzene (11.5 g) in NMP (40 mL) is added at such a rate that the reaction temperature maintains below 10° C. After stirring for 1 hour at room temperature, methanol (50 mL) and 1 M aqueous sodium hydroxide solution (39 mL) are added and the resulting mixture is stirred overnight at 100° C. Then, 4 M aqueous hydrochloric acid (100 mL) is added and the mixture is stirred for another h at 100° C. The methanol fraction is evaporated, water (200 mL) is added to the residue and the resulting mixture is extracted with ethyl acetate. The combined organic extracts are washed twice with water, twice with brine and dried (MgSO4). The solvent is evaporated and the residue is washed with methanol. The insoluble residue is separated by filtration and dried to give the white product.

Workup

  1. additioncharged with a stir bar
  2. custommaintains below 10° C
  3. stirringthe resulting mixture is stirred overnight at 100° C
  4. stirringthe mixture is stirred for another h at 100° C
  5. customThe methanol fraction is evaporated
  6. additionwater (200 mL) is added to the residue
  7. extractionthe resulting mixture is extracted with ethyl acetate
  8. washThe combined organic extracts are washed twice with water, twice with brine
  9. dry with materialdried (MgSO4)
  10. customThe solvent is evaporated
  11. washthe residue is washed with methanol
  12. customThe insoluble residue is separated by filtration
  13. customdried
  14. customto give the white product

Sources & evidence

ORD record
ord-a8f6ea36c3b442f6849ce241222ea0ea
Source dataset
uspto-grants-2013_10
Patent number
US08551957B2

Reaction notes

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