Butyl Acrylate → Butyl (2E)-3-[2-[(2,2-dimethylpropanoyl)amino]-6-(methyloxy)-3-pyridinyl]-2-propenoate

HRID 420667Notes

Reaction equation

HRID 420667 reaction equation
Br[C:2]1[C:3]([NH:10][C:11](=[O:16])[C:12]([CH3:15])([CH3:14])[CH3:13])=[N:4][C:5]([O:8][CH3:9])=[CH:6][CH:7]=1.[C:17]([O:21][CH2:22][CH2:23][CH2:24][CH3:25])(=[O:20])[CH:18]=[CH2:19].C1(C(N)C2CCCCC2)CCCCC1>C(Cl)Cl.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)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]>[CH3:13][C:12]([CH3:15])([CH3:14])[C:11]([NH:10][C:3]1[C:2](/[CH:19]=[CH:18]/[C:17]([O:21][CH2:22][CH2:23][CH2:24][CH3:25])=[O:20])=[CH:7][CH:6]=[C:5]([O:8][CH3:9])[N:4]=1)=[O:16]

Participants

7

Reactant 3

HCID 8846Butyl AcrylateHCID 10774245alpha-CyclohexylcyclohexanemethanamineHCID 58001713N-[3-Bromo-6-(methyloxy)-2-pyridinyl]-2,2-dimethylpropanamide

Product 1

HCID 58001729Butyl (2E)-3-[2-[(2,2-dimethylpropanoyl)amino]-6-(methyloxy)-3-pyridinyl]-2-propenoateYield 95.4%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 178418851HCID 178418851, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of N-[3-bromo-6-(methyloxy)-2-pyridinyl]-2,2-dimethylpropanamide (78.738 g, 274 mmol), bis(tri-t-butylphosphine)palladium(0) (1 g, 1.957 mmol) and tris(dibenzylideneacetone)dipalladium(0) (0.892 g, 0.974 mmol) in dry, degassed 1,4-dioxane (600 ml) was treated with n-butyl acrylate (47.1 ml, 329 mmol) and dicyclohexylmethylamine (64.5 ml, 302 mmol). The reaction mixture was then heated at 80° C. for 4 h and then at 120° C. for 3 h. The reaction was then evaporated and water (1000 ml) was added and the mixture was extracted with Et2O (3×500 ml). The combined organic solvents were then dried (MgSO4), filtered, evaporated to give the crude product. This was then dissolved in DCM (300 ml) and chromatographed (10-30% EtOAc:40-60 petroleum ether) and then dried in vacuo to give product as a white solid (87.412 g, 95%).

Workup

  1. customin dry
  2. customdegassed 1,4-dioxane (600 ml)
  3. customThe reaction was then evaporated
  4. additionwater (1000 ml) was added
  5. extractionthe mixture was extracted with Et2O (3×500 ml)
  6. dry with materialThe combined organic solvents were then dried (MgSO4)
  7. filtrationfiltered
  8. customevaporated
  9. customto give the crude product
  10. customchromatographed (10-30% EtOAc:40-60 petroleum ether)
  11. customdried in vacuo

Sources & evidence

ORD record
ord-c07d22eb7aa64a06bd41634d70c0ff55
Source dataset
uspto-grants-2012_01
Patent number
US08097628B2

Reaction notes

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