Methyl Acrylate → 3-(2-Methyl-pyrimidin-5-yl)-acrylic acid methyl ester

HRID 474738Notes

Reaction equation

HRID 474738 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]([CH3:8])=[N:6][CH:7]=1.[C:9]([O:13][CH3:14])(=[O:12])[CH:10]=[CH2:11].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[CH3:14][O:13][C:9](=[O:12])[CH:10]=[CH:11][C:2]1[CH:3]=[N:4][C:5]([CH3:8])=[N:6][CH:7]=1

Participants

7

Reactant 4

HCID 7294Methyl AcrylateHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 143877445-Bromo-2-methylpyrimidine

Product 1

HCID 677728483-(2-Methyl-pyrimidin-5-yl)-acrylic acid methyl esterYield 16.8%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolvent

Conditions

Temperature
150 °C

Procedure

A sealed mixture of 5-Bromo-2-methyl-pyrimidine (2.6 g, 15.03 mmol, 1 eq), methyl acrylate (1.40 eq, 1.89 ml), palladium(II)-acetate (0.013 eq, 44 mg), triphenylphosphine (0.024 eq, 95 mg), and triethylamine (1.21 eq, 2.54 ml) was heated at 150° C. (temperature on display of heating device) for 16 hours. The mixture was cooled to ambient temperature and was poured into 200 ml of water. Organic substances were extracted with EtOAc (twice, 200 ml was used in total). The gathered EtOAc layers were filtered over celite pad, were dried and the solvent was evaporated. The resulting crude was purified by chromatography on BIOTAGE SP1 purification device using 50 g normal phase silica SNAP column and EtOAc/cyclohexane solvent system (gradient 30-80% of EtOAc in 20 column volumes). Solvent from the gathered fractions of appropriate composition was evaporated and obtained was 3-(2-Methyl-pyrimidin-5-yl)-acrylic acid methyl ester (450 mg, yield=16.80%, purity=95%). MS: [M+H]+=179.13 1H NMR (300 MHz; CDCl3) δ/ppm 2.74 (s, 3H), 3.81 (s, 3H), 6.52 (d, J=16.60 Hz, 1H), 7.58 (d, J=16.60 Hz, 1H), 8.75 (s, 2H)

Workup

  1. temperature(temperature on display of heating device) for 16 hours
  2. temperatureThe mixture was cooled to ambient temperature
  3. extractionOrganic substances were extracted with EtOAc (twice, 200 ml
  4. filtrationThe gathered EtOAc layers were filtered over celite pad
  5. customwere dried
  6. customthe solvent was evaporated
  7. customThe resulting crude was purified by chromatography on BIOTAGE SP1 purification device
  8. customSolvent from the gathered fractions of appropriate composition was evaporated
  9. customobtained

Sources & evidence

ORD record
ord-4943509ceef34298ad3a3770d33066e0
Source dataset
uspto-grants-2014_01
Patent number
US08637536B2

Reaction notes

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