Dimethylformamide → Methyl 2-cyano-4-fluoro-6-methylbenzoate

HRID 2427753Notes

Reaction equation

HRID 2427753 reaction equation
[CH3:1][O:2][C:3](=[O:13])[C:4]1[C:9]([CH3:10])=[CH:8][C:7]([F:11])=[CH:6][C:5]=1I.[CH3:14][N:15](C=O)C>C(OCC)(=O)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].[Zn].[C-]#N.[Zn+2].[C-]#N>[CH3:1][O:2][C:3](=[O:13])[C:4]1[C:9]([CH3:10])=[CH:8][C:7]([F:11])=[CH:6][C:5]=1[C:14]#[N:15]

Participants

7

Reactant 2

HCID 6228DimethylformamideHCID 57949477Methyl 4-fluoro-2-iodo-6-methylbenzoate

Product 1

HCID 57949316Methyl 2-cyano-4-fluoro-6-methylbenzoateYield 91%

Reagents, catalysts & solvents 4

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 23994ZincCatalystHCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

A mixture of 2-iodo-4-fluoro-6-methyl-benzoic acid methyl ester (0.294 g, 1.0 mmol), PdCl2(dppf)2 (0.018 g, 0.025 mmol), zinc (0.002 g, 0.03 mmol), Zinc cyanide (0.234 g, 2 mmol) and DMF (3 mL) was stirred at 150° C. for 1 h. The reaction mixture was cooled to room temperature, dissolved in ethyl acetate (50 mL) and washed with water. Combined organic layer was dried (MgSO4), filtered and concentrated. Silica gel column chromatography using 10:1 hexane-ethyl acetate afforded 2-cyano-4-fluoro-6-methyl-benzoic acid methyl ester (0.175 g, 91%).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. washwashed with water
  3. dry with materialCombined organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated

Sources & evidence

ORD record
ord-541d57e05e67425b8003e3c1899f7566
Source dataset
uspto-grants-2011_06
Patent number
US07968570B2

Reaction notes

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