4-Chlorophenol → 165383-52-8

HRID 1976286Notes

Reaction equation

HRID 1976286 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.[N:9]1[N:13]2[C:14]([C@@H:18](O)[CH3:19])=[CH:15][CH:16]=[N:17][C:12]2=[N:11][CH:10]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OC(C)C)=O)=NC(OC(C)C)=O>C1(C)C=CC=CC=1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([O:8][C@@H:18]([C:14]2[N:13]3[N:9]=[CH:10][N:11]=[C:12]3[N:17]=[CH:16][CH:15]=2)[CH3:19])=[CH:4][CH:3]=1

Participants

6

Reactant 4

HCID 46844-ChlorophenolHCID 11776TriphenylphosphineHCID 75555Diisopropyl diazene-1,2-dicarboxylate2×HCID 53998193HCID 53998193, compound

Product 1

HCID 1480409165383-52-8Yield 73.6%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Conditions

Temperature
7.5 °C

Procedure

The reactor was loaded with 4-chlorophenol (58.5 g), (S)1-(1,2,4-triazolo[1,5-a]pyrimidin-7-yl)ethanol (50 g), triphenylphosphine (85 g) and toluene (900 ml). The suspension was cooled to 5-10° C. and diisopropyl azodicarboxylate (65 ml) was added over 2 hours. After complete addition of diisopropyl azodicarboxylate the solution was stirred while warming to ambient temperature. The reaction mixture was re-cooled to 0° C. and filtered. The filtrate, magnesium chloride (anhydrous; 31.1 g) and celite (25.5 g) were combined in the reactor. Toluene (500 ml) was distilled off and the remaining mixture was cooled to 0° C. The suspension formed was removed by filtration. Further magnesium chloride (2.6 g) and celite (2.5 g) were added to the filtrate. Toluene (200 ml) was removed by distillation. The residue was cooled to 0° C. and filtered. The filtercake was washed with toluene. The reactor was loaded with the filtrate, and toluene was removed by azeotropic distillation with propan-2-ol. The product crystallised from propan-2-ol at 40° C. while cooling to 20° C. The product was collected by filtration and washed with propan-2-ol. After drying, the product (R)-7-[1-(4-chlorophenoxy)ethyl]-1,2,4-triazolo[1,5-a]pyrimidine (61.1 g) was obtained (yield: 73.6%; HPLC analysis: 99.1%; chiral HPLC: ee=100%). No triphenylphosphine oxide was detectable by HPLC analysis.

Workup

  1. temperaturewhile warming to ambient temperature
  2. temperatureThe reaction mixture was re-cooled to 0° C.
  3. filtrationfiltered
  4. distillationToluene (500 ml) was distilled off
  5. temperaturethe remaining mixture was cooled to 0° C
  6. customThe suspension formed
  7. customwas removed by filtration
  8. additionFurther magnesium chloride (2.6 g) and celite (2.5 g) were added to the filtrate
  9. customToluene (200 ml) was removed by distillation
  10. temperatureThe residue was cooled to 0° C.
  11. filtrationfiltered
  12. washThe filtercake was washed with toluene
  13. customwas removed by azeotropic distillation with propan-2-ol
  14. customThe product crystallised from propan-2-ol at 40° C.
  15. temperaturewhile cooling to 20° C
  16. filtrationThe product was collected by filtration
  17. washwashed with propan-2-ol
  18. customAfter drying

Sources & evidence

ORD record
ord-973011ddbf7343898db6764e76b5b3c1
Source dataset
uspto-grants-2001_05
Patent number
US06225469B1

Reaction notes

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