1,2-Dimethoxyethane → 4-Chloro-6-(2-methoxyphenyl)pyrimidine

HRID 1890983Notes

Reaction equation

HRID 1890983 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6](Cl)[N:5]=[CH:4][N:3]=1.[CH3:9][O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1B(O)O.C(COC)OC.C([O-])(O)=O.[Na+]>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[Cl:1][C:2]1[CH:7]=[C:6]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[O:10][CH3:9])[N:5]=[CH:4][N:3]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 709434,6-DichloropyrimidineHCID 516892Sodium BicarbonateHCID 27339582-Methoxyphenylboronic acid

Product 1

HCID 152068354-Chloro-6-(2-methoxyphenyl)pyrimidineYield 75%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolvent

Procedure

4,6-dichloropyrimidine (6.0 g, 40 mmol) and 2-methoxyphenylboronic acid (4.41 g, 29 mmol) were added to a solution of dimethoxyethane (120 mL) and water (18 mL), followed by the addition of NaHCO3 (6.72 g, 80 mmol) and (PPh3)2PdCl2 (0.84 g). to this end the reaction mixture was allowed to reflux for 8 h, and then the solvent removed under reduced pressure. The residue was taken up in CH2Cl2 (100 mL), and the resulting solution washed with water, dried over anhydrous K2CO3, filtered and the solvent removed under reduced pressure. The crude product was purified by flash chropatography on silica gel (eluent CH2Cl2) and recrystallized from hexanes yielding 4-chloro-6-(2-methoxyphenyl)-pyrimidine (4.78 g; 75%).

Workup

  1. temperatureto reflux for 8 h
  2. customthe solvent removed under reduced pressure
  3. washthe resulting solution washed with water
  4. dry with materialdried over anhydrous K2CO3
  5. filtrationfiltered
  6. customthe solvent removed under reduced pressure
  7. customThe crude product was purified by flash chropatography on silica gel (eluent CH2Cl2)
  8. customrecrystallized from hexanes

Sources & evidence

ORD record
ord-064a91968a374aeaa3c28cfb943baa0c
Source dataset
uspto-grants-2013_08
Patent number
US08507498B2

Reaction notes

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