반응 #40874

반응 방정식

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

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

NaOH

→

Valsartan

수율 85.1%

용매

methanol

water

반응 조건

후처리

1. 1
   기타Nitrogen is bubbled for 5 min
2. 2
   workup.ADDITIONare added
3. 3
   기타Once 3 h
4. 4
   workup.DISTILLATIONthe methanol is distilled
5. 5
   workup.ADDITIONThe crude product is treated with 25 mL of HCl 1N and 25 mL of AcOEt
6. 6
   건조The AcOEt phase is dried with anhydrous sodium sulphate
7. 7
   workup.DISTILLATIONafter distilling the solvent the crude product
8. 8
   기타obtained
9. 9
   기타is purified by silica gel chromatography (eluent AcOEt/heptane/AcOH 1.5:5:0.2)

실험 절차

Nitrogen is bubbled for 5 min. To a mixture made up of 0.20 g (0.48 mmol) of N-(4-iodobenzyl)-N-valeryl-L-valine, 0.115 g (0.61 mmol) of 2-(1H-tetrazol-5-yl)phenylboronic acid, 0.017 g (0.024 mmol) of bis(triphenylphosphine)palladium chloride and 0.115 g (2.87 mmol) of NaOH in 2.4 mL of methanol and 0.7 mL of water are added. The reaction is heated to 70° C. under nitrogen atmosphere. Once 3 h has elapsed the reaction is considered to be completed and the methanol is distilled. The crude product 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 1.5:5:0.2) to provide 0.178 g (85%) of Valsartan.

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