4-Bromoanisole → HCID 69099531, compound

HRID 2251546Notes

Reaction equation

HRID 2251546 reaction equation
[CH2:1]([N:4]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([O:21][C:22]([F:25])([F:24])[F:23])=[CH:17][CH:16]=1)[C:5]1[N:10]=[CH:9][C:8]([C:11](=[O:13])[CH3:12])=[CH:7][CH:6]=1)[CH:2]=[CH2:3].Br[C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>CC#N.CCN(C(C)C)C(C)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:34][O:33][C:30]1[CH:31]=[CH:32][C:27](/[CH:3]=[CH:2]/[CH2:1][N:4]([CH2:14][C:15]2[CH:16]=[CH:17][C:18]([O:21][C:22]([F:25])([F:23])[F:24])=[CH:19][CH:20]=2)[C:5]2[N:10]=[CH:9][C:8]([C:11](=[O:13])[CH3:12])=[CH:7][CH:6]=2)=[CH:28][CH:29]=1

Participants

7

Reactant 3

HCID 77304-BromoanisoleHCID 80271Tri-o-tolylphosphineHCID 59643377HCID 59643377, compound

Product 1

HCID 69099531HCID 69099531, compoundYield 56.9%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 6342AcetonitrileSolventHCID 81531DiisopropylethylamineSolvent

Procedure

A mixture of 1-(6-{allyl[4-(trifluoromethoxy)benzyl]amino}pyridin-3-yl)ethanone (10 g; 28.5 mmol), 4-bromo-anisole (5.6 g; 29.9 mmol), palladium (II) acetate (0.14 g; 0.63 mmol) and tri-o-tolylphosphine (0.57 g; 1.88 mol) in 11 ml of MeCN and 8 ml of DIEA was heated to reflux overnight. Upon cooling, the mixture was concentrated and the residue partitioned between ethyl acetate and 1N NaOH. The organic phase was dried over sodium sulfate and concentrated. Purification by flash chromatography eluting with dichloromethane afforded 1-(6-{[(2E)-3-(4-methoxyphenyl)prop-2-enyl][4-(trifluoromethoxy)benzyl]amino}pyridin-3-yl)ethanone (7.4 g; 54% yield).

Workup

  1. temperaturewas heated
  2. temperatureto reflux overnight
  3. temperatureUpon cooling
  4. concentrationthe mixture was concentrated
  5. customthe residue partitioned between ethyl acetate and 1N NaOH
  6. dry with materialThe organic phase was dried over sodium sulfate
  7. concentrationconcentrated
  8. customPurification by flash chromatography
  9. washeluting with dichloromethane

Sources & evidence

ORD record
ord-d5317f7378f24b658794f5ea176f98b1
Source dataset
uspto-grants-2008_01
Patent number
US07319104B2

Reaction notes

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