Methyl iodide → Methyl 4,6-dichloro-alpha-methyl-5-pyrimidineacetate

HRID 1192427Notes

Reaction equation

HRID 1192427 reaction equation
[CH3:1][O:2][C:3](=[O:13])[CH2:4][C:5]1[C:6]([Cl:12])=[N:7][CH:8]=[N:9][C:10]=1[Cl:11].[CH3:14]I>C1COCC1>[CH3:1][O:2][C:3](=[O:13])[CH:4]([C:5]1[C:6]([Cl:12])=[N:7][CH:8]=[N:9][C:10]=1[Cl:11])[CH3:14]

Participants

4

Reactant 2

HCID 6328Methyl iodideHCID 54165419Methyl 2-(4,6-dichloropyrimidin-5-yl)acetate

Product 1

HCID 86598738Methyl 4,6-dichloro-alpha-methyl-5-pyrimidineacetateYield 83.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

To a solution of KH (30%, 13.3 g, 125 mmol) in THF (200 mL) at 0° C. was added (4,6-Dichloro-pyrimidin-5-yl)-acetic acid methyl ester (20.0 g, 90.0 mmol) and MeI (290.0 g, 8.8 mL, 141.0 mmol) in THF (200 mL) slowly. After addition, the mixture was stirred at room temperature for 30 min, and then heated to reflux for 1 hour. After cooling to 0° C., the mixture was quenched with saturated aqueous NH4Cl. The organic phase was separated and the aqueous phase was extracted with ethyl acetate (3×200 mL). The organic phase was combined and dried. After removal of the solvent, the residue was subject to column chromatography, eluted by hexane/ethyl acetate (5:1) to give 2-(4,6-Dichloro-pyrimidin-5-yl)-propionic acid methyl ester (17.6 g, 83%). 1H NMR (CDCl3, 400 MHz) δ 8.69 (s, 1H), 4.39 (dd, J=14.4 Hz, J=7.2 Hz, 1H), 3.73 (s, 3H), 1.57 (d, J=7.21 Hz, 3H).

Workup

  1. additionAfter addition
  2. temperatureheated
  3. temperatureto reflux for 1 hour
  4. temperatureAfter cooling to 0° C.
  5. customthe mixture was quenched with saturated aqueous NH4Cl
  6. customThe organic phase was separated
  7. extractionthe aqueous phase was extracted with ethyl acetate (3×200 mL)
  8. customdried
  9. customAfter removal of the solvent
  10. washeluted by hexane/ethyl acetate (5:1)

Sources & evidence

ORD record
ord-a9b39b3412ed4ae2a9a154d85714ba26
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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