反応 #40875

反応方程式

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

sodium methoxide

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

→

Valsartan

収率 58.1%

溶媒

methanol

methanol

反応条件

後処理

1. 1
   温度The reaction is cooled to 20-25° C.
2. 2
   ろ過the catalyst is filtered
3. 3
   workup.DISTILLATIONthe methanol distilled in vacuo
4. 4
   workup.DISSOLUTIONThe resulting residue is dissolved in 25 mL of water
5. 5
   洗浄following washing with 25 mL of AcOEt
6. 6
   抽出extracted twice with 20 mL of AcOEt
7. 7
   乾燥The combined phases of AcOEt are dried with anhydrous Na2SO4
8. 8
   workup.DISTILLATIONdistillation of the solvent the crude product
9. 9
   その他obtained
10. 10
    その他is purified by silica gel chromatography (eluent AcOEt/heptane/AcOH 15:5:0.2)

実験手順

A mixture made up of 1 g (2.70 mmol) of (4-bromobenzyl)-N-valeryl-L-valine, 0.513 g (2.70 mmol) of 2-(1H-tetrazol-5-yl)phenylboronic acid, 0.120 g of 5% Pd/C in paste (0.028 mmol of palladium) and 0.0084 g (0.032 mmol) of triphenylphosphine in a solution of 4.1 mL (21.5 mmol) of sodium methoxide in 30% methanol and 10 mL of methanol is heated at 70° C. for 10 h. The reaction is cooled to 20-25° C., the catalyst is filtered and the methanol distilled in vacuo. The resulting residue is dissolved in 25 mL of water and, following washing with 25 mL of AcOEt, is acidified to pH 3 with HCl 3N and extracted twice with 20 mL of AcOEt. The combined phases of AcOEt are dried with anhydrous Na2SO4 and following distillation of the solvent the crude product obtained is purified by silica gel chromatography (eluent AcOEt/heptane/AcOH 15:5:0.2) to provide 0.683 g (58%) of Valsartan.

出典