Reaktion #40874

Reaktionsgleichung

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

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

NaOH

→

Valsartan

Ausbeute 85.1%

Lösungsmittel

methanol

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeNitrogen is bubbled for 5 min
2. 2
   workup.ADDITIONare added
3. 3
   SonstigeOnce 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
   TrocknenThe AcOEt phase is dried with anhydrous sodium sulphate
7. 7
   workup.DISTILLATIONafter distilling the solvent the crude product
8. 8
   Sonstigeobtained
9. 9
   Sonstigeis purified by silica gel chromatography (eluent AcOEt/heptane/AcOH 1.5:5:0.2)

Vorschrift

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.

Quelle