2-Chloro-4,6-dimethylpyrimidine → HCID 70098742, compound

HRID 869003Notes

Reaction equation

HRID 869003 reaction equation
I[CH2:2][CH2:3][C:4]([O:6][CH3:7])=[O:5].Cl[C:9]1[N:14]=[C:13]([CH3:15])[CH:12]=[C:11]([CH3:16])[N:10]=1>C1(C)C=CC=CC=1.CN(C)C(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:16][C:11]1[CH:12]=[C:13]([CH3:15])[N:14]=[C:9]([CH2:2][CH2:3][C:4]([O:6][CH3:7])=[O:5])[N:10]=1

Participants

5

Reactant 2

HCID 205502-Chloro-4,6-dimethylpyrimidineHCID 138407Propionic acid, 3-iodo-, methyl ester

Product 1

HCID 70098742HCID 70098742, compoundYield 9.1%

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 66603805toluene N,N-dimethylacetamideSolvent

Conditions

Temperature
110 °C

Procedure

A suspension of Zn—Cu couple (3.45 g) in toluene/N,N-dimethylacetamide (14:1, 30 mL) was degassed by bubbling N2 through the suspension for 15 min. Then methyl 3-iodopropanoate (1.96 g, 9.14 mmol) was added to the suspension, and the resulting mixture was heated at 110° C. for 6 h. The reaction mixture was allowed to cool to 70° C., and 2-chloro-4,6-dimethylpyrimidine (961 mg, 6.77 mmol) and tetrakis(triphenylphosphine) palladium (235 mg, 0.203 mmol) were added. The reaction mixture was maintained at 70° C. for 22 h. Upon cooling to r.t., the mixture was filtered, and the filter cake was rinsed with ether (10 mL×3). The filtrate was extracted with 1 M hydrochloric acid (75 mL×2). The acidic extracts were basified with the addition of sodium bicarbonate, and the resulting solution was extracted with ether (75 mL×2). The combined organic layers were dried over anhydrous sodium sulfate and the solution was concentrated to give a residue, which was purified by prep-TLC to afford methyl 3-(4,6-dimethylpyrimidin-2-yl)propanoate as a pale-yellow solid (120 mg). MS (ESI): m/z 195 [M+H]+.

Workup

  1. customwas degassed
  2. customby bubbling N2 through the suspension for 15 min
  3. temperatureto cool to 70° C.
  4. temperatureThe reaction mixture was maintained at 70° C. for 22 h
  5. temperatureUpon cooling to r.t.
  6. filtrationthe mixture was filtered
  7. washthe filter cake was rinsed with ether (10 mL×3)
  8. extractionThe filtrate was extracted with 1 M hydrochloric acid (75 mL×2)
  9. additionThe acidic extracts were basified with the addition of sodium bicarbonate
  10. extractionthe resulting solution was extracted with ether (75 mL×2)
  11. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
  12. concentrationthe solution was concentrated
  13. customto give a residue, which
  14. customwas purified by prep-TLC

Sources & evidence

ORD record
ord-89831e205c2147028ccea2db9dc0fbb9
Source dataset
uspto-grants-2015_03
Patent number
US08969349B2

Reaction notes

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