2,4-Dichloropyrimidine → 4-Chloro-6-(3-fluoro-4-nitrophenoxy)pyrimidine

HRID 492859Notes

Reaction equation

HRID 492859 reaction equation
Cl[C:2]1[N:7]=[CH:6][CH:5]=[C:4]([Cl:8])[N:3]=1.[F:9][C:10]1[CH:11]=[C:12]([OH:19])[CH:13]=[CH:14][C:15]=1[N+:16]([O-:18])=[O:17].C(N(C(C)C)CC)(C)C>CN1CCCC1=O>[Cl:8][C:4]1[CH:5]=[C:6]([O:19][C:12]2[CH:13]=[CH:14][C:15]([N+:16]([O-:18])=[O:17])=[C:10]([F:9])[CH:11]=2)[N:7]=[CH:2][N:3]=1

Participants

5

Reactant 3

HCID 775312,4-DichloropyrimidineHCID 81531DiisopropylethylamineHCID 5209483-Fluoro-4-nitrophenol

Product 1

HCID 231535954-Chloro-6-(3-fluoro-4-nitrophenoxy)pyrimidineYield 30%

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Conditions

Temperature
50 °C

Procedure

After dissolving 2,6-dichloropyrimidine (5.0 g) and 3-fluoro-4-nitrophenol (6.11 g) in 1-methyl-2-pyrrolidinone (25 ml) at room temperature under a nitrogen atmosphere, diisopropylethylamine (6.81 ml) was added and the mixture was stirred for 13 hours at 50° C. The reaction mixture was cooled to room temperature and then partitioned between ethyl acetate and water. The separated organic layer was washed with water, 1N aqueous sodium hydroxide, water, 10% aqueous potassium hydrogen sulfate and brine in that order and then dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure, and then ethyl acetate (25 ml) was added to the residue to precipitate crystals. The crystals were filtered and subjected to aeration drying to provide the title compound (2.61 g, 30%) as white crystals. The filtrate was concentrated under reduced pressure, and then diethyl ether (30 ml) was added to the resultant residue and the mixture was stirred. The precipitated crystals were filtered, washed with diethyl ether (5 ml×2) and subjected to aeration drying to provide the title compound (3.98 g, 44%) as white crystals.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. custompartitioned between ethyl acetate and water
  3. washThe separated organic layer was washed with water, 1N aqueous sodium hydroxide, water, 10% aqueous potassium hydrogen sulfate and brine in that order
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. additionethyl acetate (25 ml) was added to the residue
  7. customto precipitate crystals
  8. filtrationThe crystals were filtered
  9. customdrying

Sources & evidence

ORD record
ord-371769045d9c45ada5a9b2048810f795
Source dataset
uspto-grants-2009_05
Patent number
US07531532B2

Reaction notes

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