Hydrochloric Acid → 3-Chloro-5-(6-chloro-2-fluoro-3-methylphenoxy)benzonitrile

HRID 1874782Notes

Reaction equation

HRID 1874782 reaction equation
N(OC(C)(C)C)=O.N[C:9]1[C:14]([O:15][C:16]2[CH:17]=[C:18]([CH:21]=[C:22]([Cl:24])[CH:23]=2)[C:19]#[N:20])=[C:13]([F:25])[C:12]([CH3:26])=[CH:11][CH:10]=1.[ClH:27].CCOC(C)=O>C(#N)C>[Cl:24][C:22]1[CH:21]=[C:18]([CH:17]=[C:16]([O:15][C:14]2[C:9]([Cl:27])=[CH:10][CH:11]=[C:12]([CH3:26])[C:13]=2[F:25])[CH:23]=1)[C:19]#[N:20]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 10906Tert-Butyl nitriteHCID 59451628HCID 59451628, compound

Product 1

HCID 594516403-Chloro-5-(6-chloro-2-fluoro-3-methylphenoxy)benzonitrileYield 67%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To an oven dried flask was added CuCl2 (2.5 g, 18.0 mmol). The flask was placed under high vacuum, flushed with nitrogen and acetonitrile (10 ml) was added. t-Butyl nitrite (2.7 mL, 22.5 mmol) was added dropwise. The stirred solution was placed in a an oil bath at 50° C. under gentle stream of nitrogen and 3-[(6-amino-2-fluoro-3-methylphenyl)oxy]-5-chlorobenzonitrile dissolved in acetonitrile (15 mL) was added dropwise. The reaction was stirred for 0.5 h, cooled to RT and poured into ice cold, aqueous HCl (0.5 N, 100 mL). EtOAc (100 mL) was added and the layers were separated. The aqueous layer was extracted with EtOAc (2×100 mL). The organic extracts were combined, dried over Na2SO4, filtered and evaporated. Purification was accomplished by column chromatography (hexane/EtOAc) to afford the title compound (1.8 g, 67%) as a solid. 1H NMR (400 MHz, DMSO-d6): δ ppm 7.79 (s, 1H), 7.48 (s, 1H), 7.44 (t, 1H), 7.41 (d, 1H), 7.31 (t, 1H), 2.27 (d, 3H).

Workup

  1. customTo an oven dried flask
  2. customflushed with nitrogen and acetonitrile (10 ml)
  3. additionwas added
  4. additionwas added dropwise
  5. customthe layers were separated
  6. extractionThe aqueous layer was extracted with EtOAc (2×100 mL)
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. customevaporated
  10. customPurification

Sources & evidence

ORD record
ord-3d77d83602c24b429e7e0731297523d3
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

Loading…