Ammonium Chloride → 2-(3-Bromo-4-methoxybenzoyl)-6-fluorobenzonitrile

HRID 1662210Notes

Reaction equation

HRID 1662210 reaction equation
[Cu]C#N.[Br-].[Li+].[I-].[C:7]([C:9]1[C:14]([F:15])=[CH:13][CH:12]=[CH:11][C:10]=1[Zn+])#[N:8].[Br:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=1[O:27][CH3:28])[C:21](Cl)=[O:22].[NH4+].[Cl-]>C1COCC1>[Br:17][C:18]1[CH:19]=[C:20]([CH:24]=[CH:25][C:26]=1[O:27][CH3:28])[C:21]([C:10]1[CH:11]=[CH:12][CH:13]=[C:14]([F:15])[C:9]=1[C:7]#[N:8])=[O:22]

Participants

7

Reactant 5

HCID 25517Ammonium ChlorideHCID 82050Lithium BromideHCID 27696193-Bromo-4-methoxybenzoyl chlorideHCID 178418546HCID 178418546, compoundHCID 178510276HCID 178510276, compound

Product 1

HCID 585795112-(3-Bromo-4-methoxybenzoyl)-6-fluorobenzonitrileYield 54%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of copper(I) cyanide (1.746 g, 19.50 mmol) and lithium bromide (0.98 mL, 39 mmol) in anhydrous THF (40 mL), (2-cyano-3-fluorophenyl)zinc(II) iodide (0.5M in THF, 39 mL, 19.50 mmol) was added at −78° C. followed by addition of 3-bromo-4-methoxybenzoyl chloride (5.35 g, 21.45 mmol) in THF (40 mL). The reaction mixture was allowed to reach room temperature and stirred over night. Saturated aqueous NH4Cl (40 mL) was added and the resulting mixture was concentrated under reduced pressure. The residue was diluted with water (30 ml) and extracted with DCM (3×50 mL). The combined organic extracts were passed though a phase separator (Sorbent) and concentrated under reduced pressure. The residue was purified by flash column chromatography (0-60% ethyl acetate in heptane) to afford the title compound (3.5 g, 54%).

Workup

  1. customto reach room temperature
  2. concentrationthe resulting mixture was concentrated under reduced pressure
  3. additionThe residue was diluted with water (30 ml)
  4. extractionextracted with DCM (3×50 mL)
  5. concentrationconcentrated under reduced pressure
  6. customThe residue was purified by flash column chromatography (0-60% ethyl acetate in heptane)

Sources & evidence

ORD record
ord-7a6a923b6bbd4df08b23b0cc7704fcef
Source dataset
uspto-grants-2011_10
Patent number
US08030500B2

Reaction notes

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