تفاعل #40873

معادلة التفاعل

N-(4-bromobenzyl)-N-valeryl-L-valine

sodium methoxide

2-(1H-tetrazol-5-yl)phenylboronic acid

→

Valsartan

المردود 55.6%

المذيبات

methanol

methanol

ظروف التفاعل

المعالجة

1. 1
   أخرىNitrogen is bubbled for 5 min
2. 2
   workup.ADDITIONare added
3. 3
   workup.ADDITION0.050 g of activated carbon is added
4. 4
   درجة الحرارةAfter cooling to 20-25° C. it
5. 5
   ترشيحis filtered
6. 6
   أخرىthe methanol is evaporated
7. 7
   workup.ADDITIONit is treated with 25 mL of HCl 1N and 25 mL of AcOEt
8. 8
   تجفيفThe AcOEt phase is dried with anhydrous sodium sulphate
9. 9
   workup.DISTILLATIONafter distilling the solvent the crude product
10. 10
    أخرىobtained
11. 11
    أخرىis purified by silica gel chromatography (eluent AcOEt/heptane/AcOH 15:5:0.2)

الإجراء التجريبي

Nitrogen is bubbled for 5 min. To a mixture made up of 0.50 g (1.35 mmol) of N-(4-bromobenzyl)-N-valeryl-L-valine, 0.308 g (1.52 mmol) of 2-(1H-tetrazol-5-yl)phenylboronic acid, 0.0028 g (0.016 mmol) of palladium chloride and 0.0084 g (0.032 mmol) of triphenylphosphine in a solution of 2.06 mL (13.0 mmol) of sodium methoxide in methanol al 30% and 5 mL of methanol are added. It is heated at 70° C. under nitrogen atmosphere for 5 h, 0.050 g of activated carbon is added and it is stirred at the same temperature for a further 15 min. After cooling to 20-25° C. it is filtered, the methanol is evaporated and it is treated with 25 mL of HCl 1N and 25 mL of AcOEt. The AcOEt phase is dried with anhydrous sodium sulphate and after distilling the solvent the crude product obtained is purified by silica gel chromatography (eluent AcOEt/heptane/AcOH 15:5:0.2) to provide 0.327 g (55.6%) of Valsartan.

المصدر