tert-Butyl methacrylate → tert-Butyl(2E)-3-(3-amino-4-cyanophenyl)-2-methylacrylate

HRID 1476128Notes

Reaction equation

HRID 1476128 reaction equation
[NH2:1][C:2]1[CH:9]=[C:8](Br)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].[CH3:11][C:12](=[CH2:20])[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.C1(CNCC2CCCCC2)CCCCC1>O1CCOCC1.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].C1CCCCC1.C(OCC)(=O)C>[NH2:1][C:2]1[CH:9]=[C:8](/[CH:11]=[C:12](\[CH3:20])/[C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

8

Reactant 4

HCID 11448tert-Butyl methacrylate2×HCID 83681Tris(1,1-dimethylethyl)phosphine2×HCID 4594378Bis(cyclohexylmethyl)amineHCID 99206362-Amino-4-bromobenzonitrile

Product 1

HCID 67215496tert-Butyl(2E)-3-(3-amino-4-cyanophenyl)-2-methylacrylate

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalyst2×HCID 312751,4-DioxaneSolventHCID 21867204Cyclohexane ethylacetateSolvent

Conditions

Temperature
120 °C

Procedure

Under argon, a mixture of 2.0 g (10.15 mmol) of 2-amino-4-bromobenzonitrile, 2.165 g (2.5 ml, 15.23 mmol) of tert-butyl 2-methylacrylate, 93 mg (0.10 mmol) of tris(dibenzylideneacetone)-dipalladium, 41 mg (0.20 mmol) of tri-tert-butylphosphine and 2.4 ml (11.17 mmol) of N,N-di-cyclohexylmethylamine in 20 ml of dioxane was heated to 120° C. and stirred at this temperature overnight. The reaction was checked (TLC, mobile phase cyclohexane/ethyl acetate 9:1), and another 10 mg of tris(dibenzylideneacetone)dipalladium, 10 mg of tri-tert-butylphosphine and 500 μl of tert-butyl 2-methylacrylate were then added and the mixture was stirred at 120° C. for a further 4 h. The reaction mixture was then filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethylacetate 9:1→4:1). This gave 1.375 g of the title compound (52% of theory).

Workup

  1. stirringthe mixture was stirred at 120° C. for a further 4 h
  2. filtrationThe reaction mixture was then filtered through celite
  3. concentrationthe filtrate was concentrated under reduced pressure
  4. customThe residue was purified by chromatography on silica gel (mobile phase cyclohexane/ethylacetate 9:1→4:1)

Sources & evidence

ORD record
ord-3e942cfa7f714e6aa84d8d89afc40167
Source dataset
uspto-grants-2015_04
Patent number
US09018414B2

Reaction notes

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