Dichloromethane → 2-Chloro-4-(2-methoxyphenyl)pyrimidine

HRID 2088722Notes

Reaction equation

HRID 2088722 reaction equation
Cl[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([O-])(O)=O.[Na+].[Cl:25]CCl>C(COC)OC.O.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>[Cl:25][C:4]1[N:5]=[C:6]([C:12]2[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=2[O:10][CH3:9])[CH:7]=[CH:2][N:3]=1

Participants

8

Reactant 4

HCID 6344DichloromethaneHCID 709434,6-DichloropyrimidineHCID 516892Sodium BicarbonateHCID 27339582-Methoxyphenylboronic acid

Product 1

HCID 249018822-Chloro-4-(2-methoxyphenyl)pyrimidineYield 73%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

4,6-Dichloro-pyrimidine (6 g, 0.04 mol) (Ranganathan, Subramania et al., Proceedings—Indian Academy of Sciences, Chemical Sciences (1994), 106(5), 1051-70. Maggiali, C. et al., Farmaco, Edizione Scientifica (1988), 43(3), 277-91. Gershon, Herman et al., J. of Med. Chem. (1963), 6, 87-9) and (2-methoxy-phenyl)-boronic acid (4.37 g, 0.029 mol) were dissolved in dimethoxyethane (120 mL) and water (18 mL). To this solution were added NaHCO3 (6.72 g, 0.08 mol), PdCl2(PPh3)2 (0.84 g) and allowed to reflux for 7 hrs (TLC control). Then the mixture was cooled down to room temperature and the solvents removed under reduced pressure. The obtained crude solid was dissolved in dichloromethane (100 mL), washed with water (1×100 mL), the organic layer was separated, dried over K2CO3, filtered and the solvent removed under reduced pressure. The obtained solid was further purified by flash-chromatography (eluent dichloromethane) to afford a crude product that was crystallized from hexane to yield 2-chloro-4-(2-methoxy-phenyl)-pyrimidine (4.7 g, 73%).

Workup

  1. temperatureto reflux for 7 hrs (TLC control)
  2. customthe solvents removed under reduced pressure
  3. customThe obtained crude solid
  4. washwashed with water (1×100 mL)
  5. customthe organic layer was separated
  6. dry with materialdried over K2CO3
  7. filtrationfiltered
  8. customthe solvent removed under reduced pressure
  9. customThe obtained solid was further purified by flash-chromatography (eluent dichloromethane)
  10. customto afford a crude product that
  11. customwas crystallized from hexane

Sources & evidence

ORD record
ord-9a001d19ddcf4365885a10d7ce0c31a1
Source dataset
uspto-grants-2013_05
Patent number
US08436007B2

Reaction notes

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