Dimethylformamide → Methyl 5-cyano-4-cyclobutyl-2-ethylbenzoate

HRID 541300Notes

Reaction equation

HRID 541300 reaction equation
[CH:1]1([C:5]2[C:14](I)=[CH:13][C:8]([C:9]([O:11][CH3:12])=[O:10])=[C:7]([CH2:16][CH3:17])[CH:6]=2)[CH2:4][CH2:3][CH2:2]1.[CH3:18][N:19](C)C=O>[C-]#N.[Zn+2].[C-]#N.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:18]([C:14]1[C:5]([CH:1]2[CH2:4][CH2:3][CH2:2]2)=[CH:6][C:7]([CH2:16][CH3:17])=[C:8]([CH:13]=1)[C:9]([O:11][CH3:12])=[O:10])#[N:19]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 68288985Methyl 4-cyclobutyl-2-ethyl-5-iodobenzoate2×

Product 1

HCID 68288744Methyl 5-cyano-4-cyclobutyl-2-ethylbenzoateYield 82%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a round-bottom flask, which was purged and maintained with a nitrogen atmosphere, was added a solution of methyl 4-cyclobutyl-2-ethyl-5-iodobenzoate (compound 181.4, 5.50 g, 16.0 mmol, 1.00 equiv) in N,N-dimethylformamide (150 mL). Zinc cyanide (2.78 g, 23.7 mmol, 1.50 equiv) and Pd(PPh3)4 (1.83 g, 1.59 mmol, 0.10 equiv) were added to the reaction mixture. The resulting solution was stirred at 100° C. for 15 h under nitrogen. After cooling to ambient temperature, the reaction was carefully quenched with 300 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 2×300 mL of ethyl acetate. The combined organic layers were washed with 2×300 mL of brine, dried over anhydrous sodium sulfate, and concentrated in vacuo. The residue was purified using silica gel column chromatography with ethyl acetate/petroleum ether (1:100-1:50) as eluent to furnish 3.20 g (82%) of methyl 5-cyano-4-cyclobutyl-2-ethylbenzoate as a light yellow oil.

Workup

  1. customTo a round-bottom flask, which was purged
  2. temperaturemaintained with a nitrogen atmosphere
  3. temperatureAfter cooling to ambient temperature
  4. customthe reaction was carefully quenched with 300 mL of FeSO4 (aq., sat.)
  5. additiondiluted with ethyl acetate
  6. stirringThe resulting mixture was stirred vigorously
  7. filtrationthen filtered through celite
  8. washwashed with 1 M FeSO4, water, and ethyl acetate
  9. customThe layers were separated
  10. extractionthe aqueous phase was extracted with 2×300 mL of ethyl acetate
  11. washThe combined organic layers were washed with 2×300 mL of brine
  12. dry with materialdried over anhydrous sodium sulfate
  13. concentrationconcentrated in vacuo
  14. customThe residue was purified

Sources & evidence

ORD record
ord-627376bb31b1452aad0b876854c16a58
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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