Ethyl Acetate → 6-Cyano-2-(2-tertbutylphenoxy)pyridin-3-amine

HRID 2377807Notes

Reaction equation

HRID 2377807 reaction equation
Br[C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]([CH3:18])([CH3:17])[CH3:16])[C:5]([NH2:19])=[CH:4][CH:3]=1.[Cu](C#N)[C:21]#[N:22].C(OCC)(=O)C>[C-]#N.C([N+](CC)(CC)CC)C.O1CCOCC1.CCCCCCC.CCOCC.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].C1(P(C2C=CC=CC=2)[C-]2C=CC=C2)C=CC=CC=1.[C-]1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=C1.[Fe+2]>[C:21]([C:2]1[N:7]=[C:6]([O:8][C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][C:10]=2[C:15]([CH3:18])([CH3:17])[CH3:16])[C:5]([NH2:19])=[CH:4][CH:3]=1)#[N:22]

Participants

10

Reactant 3

HCID 8857Ethyl AcetateHCID 59857539HCID 59857539, compoundHCID 178418260HCID 178418260, compound

Product 1

HCID 669875066-Cyano-2-(2-tertbutylphenoxy)pyridin-3-amineYield 162.6%

Reagents, catalysts & solvents 6

HCID 635956Ferrocene-1,1'-bis-(diphenylphosphine)CatalystHCID 3014735Tetraethylammonium cyanideCatalystHCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 3283Diethyl EtherSolventHCID 8900HeptaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
105 °C

Procedure

A mixture of 123a (1000 mg, 3.1 mmol), copper cyanide (1120 mg, 12.5 mmol), tris(dibenzylideneacetone)dipalladium(0) (114 mg, 0.12 mmol), 1,1′-Bis (diphenylphosphino) ferrocene (276 mg, 0.5 mmol) and tetraethylammonium cyanide (486 mg, 3.1 mmol) in dioxane (16 ml) was heated at 105° C. for 4.5 h. The reaction was completed as determined by TLC (30% ethyl acetate in heptane). The mixture was cooled to rt, diluted with ether (50 ml) filtered over Celite® and concentrated to give 1.3476 g of yellow foam. The foam was recrystallized from 30% ethyl acetate in heptane to give 123b (753.6 mg, 91% yield) as a brown powder. [M+H]+=268.13. 1H NMR (500 MHz, CDCl3) δ ppm 1.36 (s, 9H), 4.53 (s, 2H), 6.96 (dd, J=7.97, 4.12 Hz, 2H), 7.17 (t, J=7.42 Hz, 1H), 7.24 (m, 2H),7.44 (d, J=7.70 Hz, 1H).

Workup

  1. temperatureThe mixture was cooled to rt
  2. filtrationfiltered over Celite®
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-8b9ac5697ef14062a0355643291c2fa7
Source dataset
uspto-grants-2008_12
Patent number
US07470712B2

Reaction notes

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