4-Chlorophenol → 7-[1-(4-Chlorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidine

HRID 1976283Notes

Reaction equation

HRID 1976283 reaction equation
N(C(OC(C)C)=O)=NC(OC(C)C)=O.[N:15]1[N:19]2[C:20]([CH:24]([OH:26])[CH3:25])=[CH:21][CH:22]=[N:23][C:18]2=[N:17][CH:16]=1.[Cl:27][C:28]1[CH:33]=[CH:32][C:31](O)=[CH:30][CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl-].[Mg+2].[Cl-]>C1(C)C=CC=CC=1>[Cl:27][C:28]1[CH:33]=[CH:32][C:31]([O:26][CH:24]([C:20]2[N:19]3[N:15]=[CH:16][N:17]=[C:18]3[N:23]=[CH:22][CH:21]=2)[CH3:25])=[CH:30][CH:29]=1

Participants

7

Reactant 5

HCID 46844-ChlorophenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 5360315Magnesium ChlorideHCID 109208511-(1,2,4-Triazolo[1,5-a]pyrimidin-7-yl)ethanol

Product 1

HCID 38017397-[1-(4-Chlorophenoxy)ethyl]-[1,2,4]triazolo[1,5-a]pyrimidineYield 53%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of diisopropyl azodicarboxylate (11 g, 1.1 eq) in toluene (20 ml) was added dropwise to a stirred mixture of 1-(1,2,4-triazolo[1,5-a]pyrimidin-7-yl)ethanol (8.1 g, recrystallised from tetrahydrofuran, 49 mmol), 4-chlorophenol (6.35 g, 1 eg), triphenylphosphine (12.95 g, 1 eq) and toluene (200 ml) under nitrogen at 0-5° C. and the mixture then stirred at ambient temperature overnight. Magnesium chloride (9.5 g, -˜2 eq) was added and the stirred mixture heated under reflux for 1.5 hours, cooled to −5° C. and filtered, washing the filter pad with further toluene (2×50 ml). ml). The combined filtrate was washed with water (2×200 ml), sodium hydroxide solution (1M, 2×50 ml), and then water (2×50 ml) and then the solvent evaporated. Propan-2-ol (50 ml) was added to the residue and the solvent evaporated; this was repeated. The residue was dissolved in propan-2-ol (50 ml), seeded with a crystal of product, and left to stand at 0-5° C. for 72 hours. The product was collected by filtration, washed with cold propan-2-ol (2×20 ml) and dried in vacuo to yield 7-[1-(4-chlorophenoxy)ethyl]1,2,4-triazolo[1,5-a]pyrimidine (7.1 g, 53%), which was analysed for triphenylphosphine oxide content.

Workup

  1. temperaturethe stirred mixture heated
  2. temperatureunder reflux for 1.5 hours
  3. temperaturecooled to −5° C.
  4. filtrationfiltered
  5. washwashing the filter pad with further toluene (2×50 ml)
  6. washThe combined filtrate was washed with water (2×200 ml), sodium hydroxide solution (1M, 2×50 ml)
  7. customwater (2×50 ml) and then the solvent evaporated
  8. additionPropan-2-ol (50 ml) was added to the residue
  9. customthe solvent evaporated
  10. dissolutionThe residue was dissolved in propan-2-ol (50 ml)
  11. waitleft
  12. waitto stand at 0-5° C. for 72 hours
  13. filtrationThe product was collected by filtration
  14. washwashed with cold propan-2-ol (2×20 ml)
  15. customdried in vacuo

Sources & evidence

ORD record
ord-22c178c692dc45ad87136cbbd3a2d337
Source dataset
uspto-grants-2001_05
Patent number
US06225469B1

Reaction notes

Loading…