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

HRID 541318Notes

Reaction equation

HRID 541318 reaction equation
I[C:2]1[C:3]([CH:13]([CH3:15])[CH3:14])=[CH:4][C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8].[CH3:16][N:17](C=O)C>[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:16]([C:2]1[C:3]([CH:13]([CH3:15])[CH3:14])=[CH:4][C:5]([CH3:12])=[C:6]([CH:11]=1)[C:7]([O:9][CH3:10])=[O:8])#[N:17]

Participants

5

Reactant 2

HCID 6228DimethylformamideHCID 68288296Methyl 5-iodo-4-isopropyl-2-methylbenzoate2×

Product 1

HCID 68289240Methyl 5-cyano-4-isopropyl-2-methylbenzoateYield 83%

Reagents, catalysts & solvents 2

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

Conditions

Temperature
100 °C

Procedure

To a dried round bottom flask was added methyl 5-iodo-4-isopropyl-2-methylbenzoate (compound 198.2, 2.00 g, 6.29 mmol, 1.0 equiv), zinc cyanide (1.48 g, 12.6 mmol, 2.0 equiv), DMF (20 mL) and Pd(PPh3)4 (364 mg, 0.315 mmol, 0.05 equiv). The system was purged with nitrogen followed by argon and the mixture was heated at 100° C. for 15 hours. The reaction was allowed to cool to room temperature then diluted with ethyl acetate (50 mL) and quenched with 1 M FeSO4 (25 mL). The mixture was stirred vigorously for 40 minutes then filtered through celite and washed with 1 M FeSO4 (15 mL), water (50 mL) and ethyl acetate (150 mL). The layers were separated and the aqueous phase was extracted with ethyl acetate (50 mL). The combined organic layers were washed with brine (4×100 mL), dried (Na2SO4), filtered, and concentrated in vacuo. The product was purified by silica column chromatography (hexanes to 8% ethyl acetate) to obtain the title compound (1.14 g, 83%). 1H NMR (400 MHz, CDCl3): δ 8.19 (s, 1H), 7.25 (s, 1H), 3.91 (s, 3H), 3.37 (septet, J=6.8 Hz, 1H), 2.67 (s, 3H), 1.32 (d, J=6.8 Hz, 6H).

Workup

  1. customThe system was purged with nitrogen
  2. temperatureto cool to room temperature
  3. additionthen diluted with ethyl acetate (50 mL)
  4. customquenched with 1 M FeSO4 (25 mL)
  5. filtrationthen filtered through celite
  6. washwashed with 1 M FeSO4 (15 mL), water (50 mL) and ethyl acetate (150 mL)
  7. customThe layers were separated
  8. extractionthe aqueous phase was extracted with ethyl acetate (50 mL)
  9. washThe combined organic layers were washed with brine (4×100 mL)
  10. dry with materialdried (Na2SO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customThe product was purified by silica column chromatography (hexanes to 8% ethyl acetate)

Sources & evidence

ORD record
ord-0fc4ec2e9f3b4e8e800fa5dd22d030f6
Source dataset
uspto-grants-2014_10
Patent number
US08871790B2

Reaction notes

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