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

HRID 541272Notes

Reaction equation

HRID 541272 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]([CH3:16])[CH:6]=2)[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:14]1[C:5]([CH:1]2[CH2:4][CH2:3][CH2:2]2)=[CH:6][C:7]([CH3:16])=[C:8]([CH:13]=1)[C:9]([O:11][CH3:12])=[O:10])#[N:18]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 68288363Methyl 4-cyclobutyl-5-iodo-2-methylbenzoate2×

Product 1

HCID 68288299Methyl 5-cyano-4-cyclobutyl-2-methylbenzoate

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

A mixture of methyl 4-cyclobutyl-5-iodo-2-methylbenzoate (compound 152.3, 4.17 g, 12.64 mmol), Zn(CN)2 (2.96 g, 25.21 mmol) and Pd(PPh3)4 (0.73 g, 0.63 mmol) in DMF (30 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 mixture was quenched with saturated aq. FeSO4 (20 ml) and diluted with EtOAc (200 ml). The greenish solid was removed by filtration through celite. The filtrate was partitioned between water and EtOAc. The EtOAc layer was washed with brine, dried (Na2SO4), and concentrated. The residue was purified using column (silica gel) chromatography (hexanes:EtOAc 30:1 to 20:1). Yield: 2.55 g, white solid, 88%. 1H NMR (400 MHz, Chloroform-d) δ 8.16 (s, 1H), 7.28 (s, 1H), 3.90 (s, 3H), 3.86-3.82 (m, 1H), 2.68 (s, 3H), 2.55-2.45 (m, 2H), 2.27-2.04 (m, 3H), 1.89-1.87 (m, 1H).

Workup

  1. customwas degassed
  2. additionthe flask was filled with argon through a balloon
  3. temperatureAfter cooling to ambient temperature
  4. customthe mixture was quenched with saturated aq. FeSO4 (20 ml)
  5. additiondiluted with EtOAc (200 ml)
  6. customThe greenish solid was removed by filtration through celite
  7. customThe filtrate was partitioned between water and EtOAc
  8. washThe EtOAc layer was washed with brine
  9. dry with materialdried (Na2SO4)
  10. concentrationconcentrated
  11. customThe residue was purified

Sources & evidence

ORD record
ord-e766dd9023ee4c6a887986af27b9be37
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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