تفاعل #7031

معادلة التفاعل

biphenyl-4-carboxylic acid N′-(2-benzyloxyacetyl)hydrazide

phosphorus oxychloride

2-fluoroaniline

→

3-benzyloxymethyl-5-biphenyl-4-yl-4-(2-fluorophenyl)-4H-1,2,4-triazole

المردود 58.0%

المذيبات

ethyl acetate

ظروف التفاعل

المعالجة

1. 1
   درجة الحرارةAfter the reaction solution was cooled to ambient temperature
2. 2
   تركيزthe reaction solution was concentrated under reduced pressure
3. 3
   workup.ADDITIONTo the resulting residue was added ethyl acetate
4. 4
   غسيلthe separated organic layer was washed with aqueous 1 mol/liter sodium hydroxide solution
5. 5
   تجفيفdried over anhydrous magnesium sulfate
6. 6
   أخرىthe solvent was evaporated under reduced pressure
7. 7
   أخرىto afford an oily product
8. 8
   workup.STIRRINGstirred at 140° C. for 4 hours
9. 9
   درجة الحرارةAfter the reaction solution was cooled to ambient temperature
10. 10
    غسيلThe separated organic layer was washed with aqueous 1 mol/liter sodium hydroxide solution
11. 11
    تجفيفdried over anhydrous magnesium sulfate
12. 12
    أخرىThe solvent was evaporated under reduced pressure
13. 13
    أخرىThe resulting residue was purified by silica gel chromatography (eluent: n-hexane/ethyl acetate=3/1–1/1)

الإجراء التجريبي

To biphenyl-4-carboxylic acid N′-(2-benzyloxyacetyl)hydrazide (9.38 g) was added phosphorus oxychloride (30 ml), and stirred at 100° C. for one hour. After the reaction solution was cooled to ambient temperature, the reaction solution was concentrated under reduced pressure. To the resulting residue was added ethyl acetate, and the separated organic layer was washed with aqueous 1 mol/liter sodium hydroxide solution and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure to afford an oily product. Subsequently, 2-fluoroaniline (5 ml) and p-toluenesulfonic acid·monohydrate (200 mg) were added to the resulting oily product, and stirred at 140° C. for 4 hours. After the reaction solution was cooled to ambient temperature, ethyl acetate was added to the reaction solution. The separated organic layer was washed with aqueous 1 mol/liter sodium hydroxide solution and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. The resulting residue was purified by silica gel chromatography (eluent: n-hexane/ethyl acetate=3/1–1/1), to afford the entitled compound 3-benzyloxymethyl-5-biphenyl-4-yl-4-(2-fluorophenyl)-4H-1,2,4-triazole as pale yellow solid (6.60 g, 58%). The physico-chemical values are as follows.

المصدر