反应 #40873

反应方程式

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

sodium methoxide

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

→

Valsartan

收率 55.6%

溶剂

methanol

methanol

反应条件

后处理

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

实验过程

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.

来源