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

HRID 541358Notes

Reaction equation

HRID 541358 reaction equation
[CH:1]1([C:5]2[CH:14]=[C:13]([CH3:15])[C:12](I)=[CH:11][C:6]=2[C:7]([O:9][CH3:10])=[O:8])[CH2:4][CH2:3][CH2:2]1.[CH3:17][N:18](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:17]([C:12]1[C:13]([CH3:15])=[CH:14][C:5]([CH:1]2[CH2:4][CH2:3][CH2:2]2)=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])#[N:18]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 68288304Methyl 2-cyclobutyl-5-iodo-4-methylbenzoate

Product 1

HCID 68288958Methyl 5-cyano-2-cyclobutyl-4-methylbenzoate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 2-cyclobutyl-5-iodo-4-methylbenzoate (219.3, 3.0 g, 9.1 mmol), Zn(CN)2 (2.3 g, 19.6 mmol) and Pd(PPh3)4 (0.55 g, 0.47 mmol) in DMF (50 ml) was degassed and the flask was filled with argon through a balloon. The mixture was heated at 100° C. under argon overnight. After cooling to ambient temperature, the reaction was quenched with saturated aq. FeSO4 (20 ml) and diluted with EtOAc (200 ml). The 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 ethyl acetate. The combined organic layers were washed with brine, dried (Na2SO4), and concentrated. The residue was purified using column (silica gel) chromatography (hexanes:EtOAc 30:1 to 20:1). Yield: 2.0 g, 96%. 1H NMR (400 MHz, Chloroform-d) δ 8.03 (s, 1H), 7.34 (s, 1H), 4.26-4.13 (m, 1H), 3.89 (s, 3H), 2.59 (s, 3H), 2.46-2.32 (m, 2H), 2.16-1.98 (m, 3H), 1.90-1.78 (m, 1H).

Workup

  1. customwas degassed
  2. additionthe flask was filled with argon through a balloon
  3. temperatureAfter cooling to ambient temperature
  4. customthe reaction was quenched with saturated aq. FeSO4 (20 ml)
  5. additiondiluted with EtOAc (200 ml)
  6. filtrationthen filtered through celite
  7. washwashed with 1 M FeSO4, water and ethyl acetate
  8. customThe layers were separated
  9. extractionthe aqueous phase was extracted with ethyl acetate
  10. washThe combined organic layers were washed with brine
  11. dry with materialdried (Na2SO4)
  12. concentrationconcentrated
  13. customThe residue was purified

Sources & evidence

ORD record
ord-c018125fce2940fcb335a347a7c6e1e8
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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