Cesium carbonate → (E)-4-Methyl-6-(prop-1-enyl)pyridin-2-amine

HRID 1396467Notes

Reaction equation

HRID 1396467 reaction equation
Br[C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[C:4]([CH3:9])[CH:3]=1.CN1CC(=O)OB(/[CH:20]=[CH:21]/[CH3:22])OC(=O)C1.C(=O)([O-])[O-].[Cs+].[Cs+].O1CCOCC1>C(OCC)(=O)C.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:9][C:4]1[CH:3]=[C:2](/[CH:20]=[CH:21]/[CH3:22])[N:7]=[C:6]([NH2:8])[CH:5]=1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 221765076-Bromo-4-methylpyridin-2-amineHCID 713105776-Methyl-2-[(1E)-prop-1-en-1-yl]-1,3,6,2-dioxazaborocane-4,8-dione

Product 1

HCID 42625452(E)-4-Methyl-6-(prop-1-enyl)pyridin-2-amineYield 59.6%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
150 °C

Procedure

6-bromo-4-methylpyridin-2-amine (500 mg, 2.67 mmol), (E)-6-methyl-2-(prop-1-enyl)-1,3,6,2-dioxazaborocane-4,8-dione (1.05 g, 5.35 mmol), cesium carbonate (2.61 g, 8.02 mmol) and tetrakis(triphenylphosphine)palladium (0) (309 mg, 267 μmol) were combined with dioxane (7.4 mL and water (1.5 mL) and the mixture was heated to 150° C. for 60 min in the microwave. The reaction mixture was cooled and then diluted with ethyl acetate and water. The phases were separated and the organic phase was washed with water and brine. The organic phase was concentrated in vacuo and then purified by chromatography (silica, 20% to 60% ethyl acetate in hexanes) to give a residue that was triturated with methanol to obtain a yellow precipitate. This precipitate was collected by filtration and dried to give (E)-4-methyl-6-(prop-1-enyl)pyridin-2-amine (235 mg, 1.59 mmol, 59%) as a yellow oil. MS (EI/CI) m/z: 148.8 [M+H].

Workup

  1. temperatureThe reaction mixture was cooled
  2. customThe phases were separated
  3. washthe organic phase was washed with water and brine
  4. concentrationThe organic phase was concentrated in vacuo
  5. custompurified by chromatography (silica, 20% to 60% ethyl acetate in hexanes)
  6. customto give a residue that
  7. customwas triturated with methanol
  8. customto obtain a yellow precipitate
  9. filtrationThis precipitate was collected by filtration
  10. customdried

Sources & evidence

ORD record
ord-183fb2af481b421eaa8d9b14799bbfa7
Source dataset
uspto-grants-2014_12
Patent number
US08901124B2

Reaction notes

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