4-Chloro-2-nitrophenol → 7-[1-(4Chloro-2-nitrophenoxy)ethyl]-1,2,4-triazolo[1,5-a]pyrimidine

HRID 1976284Notes

Reaction equation

HRID 1976284 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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cl:46][C:47]1[CH:52]=[CH:51][C:50](O)=[C:49]([N+:54]([O-:56])=[O:55])[CH:48]=1.[Cl-].[Mg+2].[Cl-]>C1(C)C=CC=CC=1>[Cl:46][C:47]1[CH:52]=[CH:51][C:50]([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])=[C:49]([N+:54]([O-:56])=[O:55])[CH:48]=1

Participants

7

Reactant 5

HCID 69804-Chloro-2-nitrophenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylateHCID 5360315Magnesium ChlorideHCID 109208511-(1,2,4-Triazolo[1,5-a]pyrimidin-7-yl)ethanol

Product 1

HCID 220008327-[1-(4Chloro-2-nitrophenoxy)ethyl]-1,2,4-triazolo[1,5-a]pyrimidineYield 57.7%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent2×

Procedure

A solution of diisopropyl azodicarboxylate (12.18 g, 1.1 eq) in toluene (42 ml) was added dropwise to a stirred mixture of 1-(1,2,4-triazolo[1,5-a]pyrimidin-7-yl)ethanol (8.9 g), triphenylphosphine (14.33 g) and 4-chloro-2-nitrophenol (9.5 g, 1 eg) in toluene (140 ml) at 0-5° C. under nitrogen and the mixture stirred for 1 hour, warmed to ambient temperature and then left to stand overnight. The solvent was evaporated, and the residue dissolved in tetrahydrofuran (200 ml). Magnesium chloride (11 g; 2 eq) was added and the stirred mixture heated under reflux for 1.5 hours, cooled to ambient temperature and filtered. The filtrate solvent was evaporated and the residue partitioned between ethyl acetate (400 ml) and water (200 ml). The organic layer was washed with water (200 ml), then sodium hydroxide (1M, 100 ml) and brine (100 ml), dried (MgSO4) and the solvent evaporated. The residue was triturated with boiling propan-2-ol (200 ml), cooled and filtered to give 7-[1-(4chloro-2-nitrophenoxy)ethyl]-1,2,4-triazolo[1,5-a]pyrimidine, (10 g), 57%, mp 158° C. which was analysed for triphenylphosphine oxide content.

Workup

  1. waitleft
  2. waitto stand overnight
  3. customThe solvent was evaporated
  4. dissolutionthe residue dissolved in tetrahydrofuran (200 ml)
  5. temperaturethe stirred mixture heated
  6. temperatureunder reflux for 1.5 hours
  7. temperaturecooled to ambient temperature
  8. filtrationfiltered
  9. customThe filtrate solvent was evaporated
  10. customthe residue partitioned between ethyl acetate (400 ml) and water (200 ml)
  11. washThe organic layer was washed with water (200 ml)
  12. dry with materialsodium hydroxide (1M, 100 ml) and brine (100 ml), dried (MgSO4)
  13. customthe solvent evaporated
  14. customThe residue was triturated with boiling propan-2-ol (200 ml)
  15. temperaturecooled
  16. filtrationfiltered

Sources & evidence

ORD record
ord-c877f4263632449eaf70d1906fcbd92b
Source dataset
uspto-grants-2001_05
Patent number
US06225469B1

Reaction notes

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