Methyl iodide → 4-Acetyl-2-bromo-6-chloro-3-methoxybenzonitrile

HRID 1499895Notes

Reaction equation

HRID 1499895 reaction equation
[Br:1][C:2]1[C:3]([OH:13])=[C:4]([C:10](=[O:12])[CH3:11])[CH:5]=[C:6]([Cl:9])[C:7]=1F.[C-:14]#[N:15].[K+].I[CH3:18].C(=O)([O-])[O-].[K+].[K+]>CN(C)C=O.C(OCC)(=O)C>[C:10]([C:4]1[CH:5]=[C:6]([Cl:9])[C:7]([C:14]#[N:15])=[C:2]([Br:1])[C:3]=1[O:13][CH3:18])(=[O:12])[CH3:11]

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 9032Potassium CyanideHCID 11430Potassium CarbonateHCID 866668921-(3-Bromo-5-chloro-4-fluoro-2-hydroxyphenyl)ethanone

Product 1

HCID 866778184-Acetyl-2-bromo-6-chloro-3-methoxybenzonitrileYield 76.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

1-(3-Bromo-5-chloro-4-fluoro-2-hydroxyphenyl)ethanone (2.0 g, 7.5 mmol, Example 43, Step 1) was combined with potassium cyanide (0.58 g, 9.0 mmol) in N,N-dimethylformamide (16 mL) and heated to 85° C. in an oil bath. After heating for 18 hrs, the reaction was allowed to cool to room temperature and iodomethane (0.90 mL, 11 mmol) and potassium carbonate (2.1 g, 15 mmol) were added. The reaction was heated to 65° C. and monitored by LC/MS. After heating for 3 hrs the reaction was complete and allowed to cool to room temperature, then taken up in ethyl acetate and washed with water, brine, and dried over magnesium sulfate. The resultant solution was concentrated to give the crude product as a dark oil. The product was purified by FCC on silica gel eluting hexane:ethyl acetate gradient to give 4-acetyl-2-bromo-6-chloro-3-methoxybenzonitrile (1.65 g, 75%) as a solid residue. LCMS calculated for C10H8BrClNO2(M+H)+: m/z=287.9, 289.9; found: 288.1, 290.0.

Workup

  1. temperatureAfter heating for 18 hrs
  2. temperatureto cool to room temperature
  3. temperatureThe reaction was heated to 65° C.
  4. temperatureAfter heating for 3 hrs the reaction
  5. temperatureto cool to room temperature
  6. washwashed with water, brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationThe resultant solution was concentrated
  9. customto give the crude product as a dark oil
  10. customThe product was purified by FCC on silica gel
  11. washeluting hexane

Sources & evidence

ORD record
ord-983b0926d5d14acbb4c53fd5b765c4b8
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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