Dimethylformamide → 4-Acetyl-2-bromo-6-chloro-3-ethoxybenzonitrile

HRID 1499735Notes

Reaction equation

HRID 1499735 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-]#N.[K+].C[N:18]([CH3:21])C=O.I[CH2:23][CH3:24].C(=O)([O-])[O-].[K+].[K+]>C(OCC)(=O)C>[C:10]([C:4]1[CH:5]=[C:6]([Cl:9])[C:7]([C:21]#[N:18])=[C:2]([Br:1])[C:3]=1[O:13][CH2:23][CH3:24])(=[O:12])[CH3:11]

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 6340IodoethaneHCID 9032Potassium CyanideHCID 11430Potassium CarbonateHCID 866668921-(3-Bromo-5-chloro-4-fluoro-2-hydroxyphenyl)ethanone

Product 1

HCID 866668914-Acetyl-2-bromo-6-chloro-3-ethoxybenzonitrileYield 50.7%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
85 °C

Procedure

1-(3-Bromo-5-chloro-4-fluoro-2-hydroxyphenyl)ethanone (2.0 g, 7.5 mmol) was combined with potassium cyanide (0.58 g, 9.0 mmol) in N,N-dimethylformamide (16 mL, 210 mmol) and heated to 85° C. in an oil bath. After heating for 18 hours, the reaction was allowed to cool to room temperature and iodoethane (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 hours 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 flash column chromatography on silica gel eluting hexane:ethyl acetate gradient to give 4-acetyl-2-bromo-6-chloro-3-ethoxybenzonitrile (1.15 gm, 50%) as a solid residue, LCMS calculated for C1iH9BrClNO2(M+H)+: m/z=301.9, 303.9; found: (no ionization)

Workup

  1. temperatureAfter heating for 18 hours
  2. temperatureto cool to room temperature
  3. temperatureThe reaction was heated to 65° C.
  4. temperatureAfter heating for 3 hours 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 flash column chromatography on silica gel
  11. washeluting hexane

Sources & evidence

ORD record
ord-9b68a88d54d34ddc8bbcb7426c257950
Source dataset
uspto-grants-2015_12
Patent number
US09199982B2

Reaction notes

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