Acrylonitrile → (E)-Methyl 5-chloro-2-(2-cyanovinyl)benzoate

HRID 84932Notes

Reaction equation

HRID 84932 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:9]([Cl:12])=[CH:8][C:3]=1[C:4]([O:6][CH3:7])=[O:5].[C:13](#[N:16])[CH:14]=[CH2:15].C([O-])(=O)C.[Na+].C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C.C[Si](C=[N+]=[N-])(C)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CN(C)C=O>[Cl:12][C:9]1[CH:10]=[CH:11][C:2](/[CH:15]=[CH:14]/[C:13]#[N:16])=[C:3]([CH:8]=1)[C:4]([O:6][CH3:7])=[O:5]

Participants

8

Reactant 5

HCID 7855AcrylonitrileHCID 80271Tri-o-tolylphosphineHCID 167693TrimethylsilyldiazomethaneHCID 280500Methyl 2-Bromo-5-chlorobenzoateHCID 517045Sodium Acetate

Product 1

HCID 86647795(E)-Methyl 5-chloro-2-(2-cyanovinyl)benzoate

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To an N,N-dimethylformamide solution (100 mL) of methyl 2-bromo-5-chlorobenzoate (25, 100 mmol) was added palladium(II) acetate (480 mg, 2.1 mmol) tri(o-tolyl)phosphine (1.2 g, 3.9 mmol), acrylonitrile (6 g, 113 mmol), and anhydrous sodium acetate (10 g, 122 mmol). The mixture was heated at 120° C. Additional palladium(II) acetate (224 mg, 1 mmol) and tri(o-tolyl)phosphine (600 mg, 2 mmol) were added, after 36 hours. The mixture was heated at 120° C. for 24 hours. N,N-Dimethylformamide was removed in vacuo and the remaining mixture was quenched with 1 N HCl(aq) and extracted with ethyl acetate. The ethyl acetate extracts were concentrated and the residue was dissolved in 1:1 dichloromethane:methanol (50 mL). (Trimethylsilyl)diazomethane (30 mL, 2 N in diethyl ether, 60 mmol) was added dropwise. After stirring overnight, the mixture was quenched with acetic acid, concentrated under reduced pressure and purified by silica gel column chromatography eluting with 2:1 hexanes:ethyl acetate to afford the title compound (2:1 E/Z isomers). 1H NMR (E isomer, Example 45A, 300 MHz, DMSO-d6) δ ppm 8.08 (d, J=16.2 Hz, 1H), 7.91 (d, J=2.1 HZ, 1H), 7.84 (d, J=8.7 HZ, 1H), 7.78 (dd, J=2.1, 8.4 Hz, 1H), 6.45 (d, J=16.5 Hz, 1H), and 3.88 (s, 3H).

Workup

  1. temperatureThe mixture was heated at 120° C. for 24 hours
  2. customN,N-Dimethylformamide was removed in vacuo
  3. customthe remaining mixture was quenched with 1 N HCl(aq)
  4. extractionextracted with ethyl acetate
  5. concentrationThe ethyl acetate extracts were concentrated
  6. dissolutionthe residue was dissolved in 1:1 dichloromethane
  7. customthe mixture was quenched with acetic acid
  8. concentrationconcentrated under reduced pressure
  9. custompurified by silica gel column chromatography
  10. washeluting with 2:1 hexanes

Sources & evidence

ORD record
ord-2bfc6e46b20846a8b2c122ecc14fb9c3
Source dataset
uspto-grants-2014_09
Patent number
US08846951B2

Reaction notes

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