反応 #40873

反応方程式

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

sodium methoxide

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

→

Valsartan

収率 55.6%

溶媒

methanol

methanol

反応条件

後処理

1. 1
   その他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
   ろ過is filtered
6. 6
   その他the methanol is evaporated
7. 7
   workup.ADDITIONit is treated with 25 mL of HCl 1N and 25 mL of AcOEt
8. 8
   乾燥The AcOEt phase is dried with anhydrous sodium sulphate
9. 9
   workup.DISTILLATIONafter distilling the solvent the crude product
10. 10
    その他obtained
11. 11
    その他is purified by silica gel chromatography (eluent AcOEt/heptane/AcOH 15:5:0.2)

実験手順

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.

出典