Acrylonitrile → Dimethyl 4-(2-cyanovinyl)isophthalate

HRID 715999Notes

Reaction equation

HRID 715999 reaction equation
Br[C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:12]([O:14][CH3:15])=[O:13].[C:16](#[N:19])[CH:17]=[CH2:18].C1(CNCC2CCCCC2)CCCCC1.C(P(C(C)(C)C)C(C)(C)C)(C)(C)C>C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C(OCC)(=O)C.CCCCCC.O1CCOCC1>[C:16]([CH:17]=[CH:18][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[C:12]([O:14][CH3:15])=[O:13])#[N:19]

Participants

9

Reactant 4

HCID 7855AcrylonitrileHCID 83681Tris(1,1-dimethylethyl)phosphineHCID 2824912Dimethyl 4-bromoisophthalateHCID 4594378Bis(cyclohexylmethyl)amine

Product 1

HCID 66819156Dimethyl 4-(2-cyanovinyl)isophthalate

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolventHCID 21226206Ethyl acetate hexaneSolvent

Conditions

Temperature
80 °C

Procedure

A microwave vial was charged with dimethyl 4-bromoisophthalate (Example 88A, 500 mg, 1.83 mmol), acrylonitrile (117 mg, 2.20 mmol), N,N-dicyclohexylmethylamine (429 mg, 2.20 mmol), tri-tert-butylphosphine (0.11 mL, 0.11 mmol, 1.0 M in toluene), tris(dibenzylideneacetone)dipalladium(0) (50.3 mg, 0.055 mmol), and 1,4-dioxane (1.4 mL) under nitrogen. The reaction mixture was heated to 80° C. in an oil bath for 4 hours. Reaction was complete as indicated by thin layer chromatography (40% ethyl acetate/hexane). The reaction mixture was cooled to room temperature and diluted with ethyl acetate. Filtration removed HBr salts. The filtrate was concentrated. The residue was triturated with ethyl acetate/hexane (1:6) to provide dimethyl 4-(2-cyanovinyl)isophthalate as a mixture of trans and cis isomers (ratio 5.5:1) which was used in next step without further purification.

Workup

  1. customReaction
  2. temperatureThe reaction mixture was cooled to room temperature
  3. filtrationFiltration
  4. customremoved HBr salts
  5. concentrationThe filtrate was concentrated
  6. customThe residue was triturated with ethyl acetate/hexane (1:6)

Sources & evidence

ORD record
ord-200f89808d2f43f8a0ad7abb8773d235
Source dataset
uspto-grants-2015_11
Patent number
US09187483B2

Reaction notes

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