Dimethylformamide → Methyl 5-cyano-4-cyclopropyl-2-methylbenzoate

HRID 541266Notes

Reaction equation

HRID 541266 reaction equation
[CH:1]1([C:4]2[C:13](I)=[CH:12][C:7]([C:8]([O:10][CH3:11])=[O:9])=[C:6]([CH3:15])[CH:5]=2)[CH2:3][CH2:2]1.[CH3:16][N:17](C=O)C>[C-]#N.[C-]#N.[Zn+2].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[C:16]([C:13]1[C:4]([CH:1]2[CH2:3][CH2:2]2)=[CH:5][C:6]([CH3:15])=[C:7]([CH:12]=1)[C:8]([O:10][CH3:11])=[O:9])#[N:17]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 68288233Methyl 4-cyclopropyl-5-iodo-2-methylbenzoate2×

Product 1

HCID 68288751Methyl 5-cyano-4-cyclopropyl-2-methylbenzoateYield 81%

Reagents, catalysts & solvents 2

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 4-cyclopropyl-5-iodo-2-methylbenzoate (compound 142.2, 2.00 g, 6.01 mmol, 1.00 equiv, 95%) in DMF (16 mL) was added Zn(CN)2 (890 mg, 7.58 mmol, 1.27 equiv) and Pd(PPh3)4 (731 mg, 0.630 mmol, 0.11 equiv). The resulting solution was stirred at 100° C. under nitrogen overnight. After cooling to ambient temperature, the reaction was then quenched by the addition of 100 mL of FeSO4 (aq., sat.) and diluted with ethyl acetate. The resulting mixture was stirred vigorously then filtered through celite and washed with 1 M FeSO4, water, and ethyl acetate. The layers were separated and the aqueous phase was extracted with 2×100 mL of ethyl acetate. The combined organic phases were dried over anhydrous sodium sulfate and concentrated in vacuo. The residue was purified via silica gel column chromatography with ethyl acetate/petroleum ether (1/50) as eluent to yield 1.10 g (81%) of methyl 5-cyano-4-cyclopropyl-2-methylbenzoate as a light yellow oil.

Workup

  1. temperatureAfter cooling to ambient temperature
  2. customthe reaction was then quenched by the addition of 100 mL of FeSO4 (aq., sat.)
  3. additiondiluted with ethyl acetate
  4. stirringThe resulting mixture was stirred vigorously
  5. filtrationthen filtered through celite
  6. washwashed with 1 M FeSO4, water, and ethyl acetate
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted with 2×100 mL of ethyl acetate
  9. dry with materialThe combined organic phases were dried over anhydrous sodium sulfate
  10. concentrationconcentrated in vacuo
  11. customThe residue was purified via silica gel column chromatography with ethyl acetate/petroleum ether (1/50) as eluent

Sources & evidence

ORD record
ord-4be2e89b9dd24c85a1f44c52da01ea3d
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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