Ethyl Acrylate → Ethyl (E)-3-(6-amino-4-methylpyridin-3-yl)acrylate

HRID 225883

Reaction equation

HRID 225883 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([CH3:8])[C:5](Br)=[CH:4][N:3]=1.[C:10]([O:14][CH2:15][CH3:16])(=[O:13])[CH:11]=[CH2:12].CCN(C(C)C)C(C)C.C1(C)C=CC=CC=1P(C1C=CC=CC=1C)C1C=CC=CC=1C>C(#N)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[NH2:1][C:2]1[N:3]=[CH:4][C:5](/[CH:12]=[CH:11]/[C:10]([O:14][CH2:15][CH3:16])=[O:13])=[C:6]([CH3:8])[CH:7]=1

Participants

7

Reactant 4

HCID 8821Ethyl AcrylateHCID 80271Tri-o-tolylphosphineHCID 81531DiisopropylethylamineHCID 8176952-Amino-5-bromo-4-methylpyridine

Product 1

HCID 57440845Ethyl (E)-3-(6-amino-4-methylpyridin-3-yl)acrylateYield 59%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 7854PropionitrileSolvent

Procedure

To a stirred solution of 2-amino-5-bromo-4-methylpyridine (10 g, 54 mmole) in propionitrile (50 mL) was added ethyl acrylate (17 mL, 157 mmole), DIEA (19 mL, 106 mmole), palladium(II) acetate (0.61 g, 2.7 mmole) and tri-o-tolylphosphine (1.64 g, 5.4 mmole). The reaction was purged with argon and heated at reflux for 6 hr, then was cooled to RT and concentrated to dryness under vacuum. The resulting residue was taken up in ethyl acetate and filtered through a pad of silica gel. The filtrate was concentrated and the remaining residue was triturated with 1:1 Et2O/petroleum ether (50 mL), filtered, and dried under vacuum to give the title compound (6.50 g, 59%) as a pale yellow solid: 1H NMR (400 MHz, DMSO-d6) δ 8.31 (s, 1 H), 7.66 (d, J=16.0 Hz, 1 H), 6.40 (br s, 2 H), 6.32 (d, J=16.0 Hz, 1 H), 6.28 (s, 1 H), 4.15 (q, 2 H), 2.24 (s, 3 H), 1.24 (t, 3 H).

Workup

  1. customThe reaction was purged with argon
  2. temperatureheated
  3. temperatureat reflux for 6 hr
  4. concentrationconcentrated to dryness under vacuum
  5. filtrationfiltered through a pad of silica gel
  6. concentrationThe filtrate was concentrated
  7. customthe remaining residue was triturated with 1:1 Et2O/petroleum ether (50 mL)
  8. filtrationfiltered
  9. customdried under vacuum

Sources & evidence

ORD record
ord-11ef8d546f2942e882ed85f1ac542b6a
Source dataset
uspto-grants-2009_07
Patent number
US07557125B2

Linked notes

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